Hepatoprotective effect of pentoxifylline against D-galactosamine-induced hepatotoxicity in rats

array:24 ["pii" => "S166526811931751X" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31751-X" "estado" => "S300" "fechaPublicacion" => "2009-10-01" "aid" => "71413" "copyright" => "Fundación Clínica Médica Sur, A.C." "copyrightAnyo" => "2009" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2009;8:364-70" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 61 "formatos" => array:3 [ "EPUB" => 12 "HTML" => 28 "PDF" => 21 ] ] "itemSiguiente" => array:19 [ "pii" => "S1665268119317521" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31752-1" "estado" => "S300" "fechaPublicacion" => "2009-10-01" "aid" => "71414" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2009;8:371-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 60 "formatos" => array:3 [ "EPUB" => 13 "HTML" => 21 "PDF" => 26 ] ] "en" => array:11 [ "idiomaDefecto" => true "titulo" => "Acute treatment of constant darkness increases the efficiency of ATP synthase in rat liver mitochondria" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "371" "paginaFinal" => "376" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1394 "Ancho" => 2079 "Tamanyo" => 332695 ] ] "descripcion" => array:1 [ "en" => "ATP synthase activity (A), ATPase activity (B), % ACMA fluorescence quenching (C) and excimer/monomer intensity fluorescence ratio (D) in mitochondria (A) and submitochondrial particles (B, C, D) from rats kept under constant darkness and normal cycles of light/dark. Enzymatic activities and membrane fluidity determinations were done as described in Methods. The data shown are mean ± S.E. *p < 0.05." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana Laura Ramírez-Iñiguez, Genaro Gabriel Ortiz, Mohammed El Hafidi, Ana Rosa Rincón-Sánchez, Ernesto Macías-Rodríguez, Fermín Paul Pacheco-Moisés" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Ana" "apellidos" => "Laura Ramírez-Iñiguez" ] 1 => array:2 [ "nombre" => "Genaro" "apellidos" => "Gabriel Ortiz" ] 2 => array:2 [ "nombre" => "Mohammed" "apellidos" => "El Hafidi" ] 3 => array:2 [ "nombre" => "Ana" "apellidos" => "Rosa Rincón-Sánchez" ] 4 => array:2 [ "nombre" => "Ernesto" "apellidos" => "Macías-Rodríguez" ] 5 => array:2 [ "nombre" => "Fermín" "apellidos" => "Paul Pacheco-Moisés" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119317521?idApp=UINPBA00004N" "url" => "/16652681/0000000800000004/v1_201907070733/S1665268119317521/v1_201907070733/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268119317508" "issn" => "16652681" "doi" => "10.1016/S1665-2681(19)31750-8" "estado" => "S300" "fechaPublicacion" => "2009-10-01" "aid" => "71412" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2009;8:359-63" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 178 "formatos" => array:3 [ "EPUB" => 9 "HTML" => 140 "PDF" => 29 ] ] "en" => array:10 [ "idiomaDefecto" => true "titulo" => "The safety and feasibility of large volume paracentesis performed by an experienced nurse practitioner" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "359" "paginaFinal" => "363" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Nooman Gilani, Nayan Patel, Richard D Gerkin, Francisco C Ramirez, Erin E Tharalson, Kandarp Patel" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Nooman" "apellidos" => "Gilani" ] 1 => array:2 [ "nombre" => "Nayan" "apellidos" => "Patel" ] 2 => array:2 [ "nombre" => "Richard D" "apellidos" => "Gerkin" ] 3 => array:2 [ "nombre" => "Francisco C" "apellidos" => "Ramirez" ] 4 => array:2 [ "nombre" => "Erin E" "apellidos" => "Tharalson" ] 5 => array:2 [ "nombre" => "Kandarp" "apellidos" => "Patel" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119317508?idApp=UINPBA00004N" "url" => "/16652681/0000000800000004/v1_201907070733/S1665268119317508/v1_201907070733/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "titulo" => "Hepatoprotective effect of pentoxifylline against D-galactosamine-induced hepatotoxicity in rats" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "364" "paginaFinal" => "370" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Ashraf Taye, Mohamed A. El-Moselhy, Magdy K.A. Hassan, Hanaa M. Ibrahim, Aliaa F. Mohammed" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Ashraf" "apellidos" => "Taye" "email" => array:1 [ 0 => "Ashraf_taye70@yahoo.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] 1 => array:3 [ "nombre" => "Mohamed A." "apellidos" => "El-Moselhy" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] ] ] 2 => array:3 [ "nombre" => "Magdy K.A." "apellidos" => "Hassan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "**" "identificador" => "aff2" ] ] ] 3 => array:3 [ "nombre" => "Hanaa M." "apellidos" => "Ibrahim" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "**" "identificador" => "aff2" ] ] ] 4 => array:3 [ "nombre" => "Aliaa F." "apellidos" => "Mohammed" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "aff1" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Pharmacology & Toxicology, Faculty of Pharmacy, Minia University" "etiqueta" => "*" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Department of Physiology, Faculty of Medicine, Minia University" "etiqueta" => "**" "identificador" => "aff2" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "f0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 744 "Ancho" => 2077 "Tamanyo" => 226078 ] ] "descripcion" => array:1 [ "en" => "Effect of D-Gal on hepatic lipid peroxidation and total nitrites in normal rats and those pretreated with PTX, SYM and their combination. A. Effect of D-Gal on the hepatic lipid peroxidation in normal rats pretreated with either PTX or SYM or their combination. B. Effect of D-Gal on the hepatic total nitrites in normal rats pretreated with PTX and SYM individually or in concurrent administration. Values of each bar represent the mean ± SEM of 7 observations. * Statistically significant from the control group at the significance level p < 0.05. #, f, δ Statistically significant of PTX, SYM and (PTX and SYM) versus D-Gal-treated group, respectively, at the significance level p < 0.05. MDA: Malondialdhyde and other symbols as in <a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>." ] ] ] "textoCompleto" => "IntroductionLiver injury can be caused by different agents, such as viruses, chemicals, alcohol, and auto-immune diseases<a class="elsevierStyleCrossRef" href="#bib0005">1</a> D-galactosamine (D-Gal) is a well established hepatotoxicant, it induces a diffuse type of liver injury closely resembling human viral hepatitis<a class="elsevierStyleCrossRef" href="#bib0010">2</a> and acute self-limiting hepatitis with necrosis, inflammation and regeneration, resembling a drug-induced disease in humans.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> The toxicity of D-Gal is mainly related to the depletion of uridine pools that are associated with limited ribonucleic acid (RNA) and protein synthesis, thus altering hepatocellular function.<a class="elsevierStyleCrossRef" href="#bib0020">4</a>Different pharmacological compounds have been tested to reduce acute or chronic inflammatory responses, which may damage liver function. It has been demonstrated that phosphodiesterase inhibitors may be protective in various liver injury models.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>,<a class="elsevierStyleCrossRef" href="#bib0030">6</a> Pentoxifylline (PTX) (non-selective phosphodiesterase inhibitor) is a methyl xanthine derivative that has been used for its regulatory effect on blood flow. PTX increases the flexibility of red and white blood cells, reduces the blood viscosity by decreasing plasma fibrinogen concentrations and decrease platelet aggregation and thrombus formation. Polymorphonuclear leukocyte-mediated effects, such as superoxide production, chemotaxis, phagocytosis and tumor necrosis factor (TNF) production are inhibited by PTX.<a class="elsevierStyleCrossRef" href="#bib0035">7</a>Silymarin (SYM) from milk thistle is a hepatoprotective drug was widely used in the world. SYM may reduce free radical production and lipid peroxidation in the setting of hepatotoxicity as it has powerful antioxidant properties.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> SYM may act through its ability for toxin blockade; it may bind to the hepatocyte cell membrane receptor site, inhibiting binding of toxins to these sites.The aim of the present study was to examine the putative hepatoprotective effects of PTX against hepatotoxicity induced by D-Gal and elucidate the underlying mechanisms involved in this protection, as a sole effect or synergistic with SYM.Material and MethodsAnimalsAnimals used in the present study were male albino rats (8 weeks of age) weighing 180-200 g. Animals were kept under constant environmental conditions throughout the period of the experiment. Animals were exposed to dark/light cycle of 12:12 hours. Experiments were conducted in accordance with the guidelines for animal care of the United States Naval Medical Research Centre, Unit No. 3, Abbaseya, Cairo, Egypt, accredited by the Association for Assessment and Accreditation of Laboratory Animal Care international (AAALAC international).Experimental proceduresAll animals were fed standard animal chow along the period of the experiment (21 days). After the acclimatization period, the rats were divided into five groups, each of 12 rats. Firstly, control group; in which animals received saline 0.5 mL/day i.p. for 3 weeks. Second, D-GAL-treated group; in which animals received saline 0.5 mL/day i.p. for 3 weeks and at 21st day received a single dose of D-GAL. Third, PTX-treated group; animals received PTX (100 mg/kg/day, i.p.) dissolved in 0.5 mL saline for 3 weeks. Fourth, SYM-treated group; in which animals received SYM (100 mg/kg/day, oral) suspended in 0.5 mL 0.1% starch solution for 3 weeks. Fifth, PTX + SYL group; animals received PTX followed by simultaneous administration of SYM for 3 weeks by the same previous doses as previously described.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>All groups except group 1 received at 21st day a single dose of D-Gal (800 mg/kg, i.p.) once in the morning. At the end of the study, the animals were sacrificed and blood was collected for separation of sera. The livers were isolated, washed off blood and connective tissue was removed then portions of liver tissues were separated and kept in 10% formalin for histopathological examination.Immediately, the rest of liver tissues were immediately flash-frozen in liquid nitrogen and stored at - 80 °C. Kits used for determination of malonaldahyde (MDA) levels (Biodiagnostic, Egypt) as a marker of lipid peroxides,<a class="elsevierStyleCrossRef" href="#bib0055">11</a> tissue nitrite as an indicator of nitric oxide (Biodiagnostic, Egypt), albumin (DP International, Egypt), alkaline phosphatase (ALP), and total protein concentrations (Spectrum Diagnostics, Egypt), superoxide dismutase (SOD) and catalase (CAT) enzymes<a class="elsevierStyleCrossRef" href="#bib0060">12</a> (Biodiagnostic, Egypt). In addition, serum albumin levels and ALP activities were measured in sera of all the experimental animals.Histopathological examinationSmall pieces of the livers fixed in 10% buffered neutral formalin were processed for embedding in paraffin. Sections of 5-6 mm thickness were stained with hematoxylin and eosin, examined for histopathological changes.Statistical analysisResults were expressed as means ± standard error of the mean (SEM) and were analyzed for statistically significant difference using one-way analysis of variance (ANOVA) followed by the Tukey-Kramar post analysis test. P values less than 0.05 were considered significant.ResultsEffects of PTX on the serum albumin and ALP levelsD-Gal exhibited a significant reduction of serum albumin level when compared to control rats. However, the individual or combined administration of either PTX or SYM resulted in a significant elevation in serum albumin level nearly to the control level (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1A</a>). Administration of D-Gal resulted in a significant elevation of serum ALP activity in comparison to the control rats. Meanwhile, the single or combined administration of either PTX or SYM exerted a marked reduction in the serum ALP activity to the normal level (<a class="elsevierStyleCrossRef" href="#f0005">Figure 1B</a>).<elsevierMultimedia ident="f0005"></elsevierMultimedia>Effect of PTX on the hepatic oxidative stress markersD-Gal produced a significant decrease of CAT activity when compared to control rats. Pretreatment with either PTX or SYM significantly increased CAT activity of liver tissue compared to D-Gal-treated group. Combined administration of PTX and SYM significantly increased the hepatic CAT activity compared to D-Gal-treated group (<a class="elsevierStyleCrossRef" href="#f0010">Figure 2A</a>). The activity of SOD was significantly reduced in D-Gal group as compared to control rats. In PTX pretreated group, a significant increase of SOD activity was observed compared to D-Gal-treated group. Meanwhile, pretreatment with SYM or (PTX + SYM) significantly increased SOD activity when compared to D-Gal-treated group (<a class="elsevierStyleCrossRef" href="#f0010">Figure 2B</a>).<elsevierMultimedia ident="f0010"></elsevierMultimedia>Effect of PTX on the hepatic lipid peroxidation and total nitrite levelsIntraperitoneal administration of D-Gal significantly elevated the hepatic tissue MDA concentration (a biochemical marker of lipid peroxidation) to about two-fold of the value observed in control group (<a class="elsevierStyleCrossRef" href="#f0015">Figure 3A</a>).<elsevierMultimedia ident="f0015"></elsevierMultimedia>On the other hand, the total hepatic nitrite level was significantly elevated in D-Gal treated groups compared to the control group. However, the single or combined administration of PTX and SYM significantly restored the elevated hepatic total nitrites to the normal level (<a class="elsevierStyleCrossRef" href="#f0015">Figure 3B</a>).Histopathological examinationTo verify the biochemical changes in liver, the histopathological examination of liver both of the control and treated rats was performed. The liver of the control group was normal with no evidence of any microscopic abnormalities (<a class="elsevierStyleCrossRef" href="#f0020">Figure 4A</a>). In D-Gal-treated group, microscopically, vasculitis, represented by congested blood vessels and perivascular edema and few lymphocytes infiltrations was noticed. Thickening and hyalinization of the tunica media of hepatic arterioles were observed (<a class="elsevierStyleCrossRef" href="#f0020">Figure 4B</a>). In PTX group, microscopically, some portal areas showed congested blood vessels and leukocyte margination and emigration besides mild hyperplasia of the epithelial lining of the bile ducts and few round cell infiltrations (<a class="elsevierStyleCrossRef" href="#f0015">Figure 4C</a>). In SYM-treated group, few round cells (mainly of lymphocytes) in the portal areas and the interstitial tissue were detected (<a class="elsevierStyleCrossRef" href="#f0020">Figure 4D</a>).<elsevierMultimedia ident="f0020"></elsevierMultimedia>DiscussionThe current study investigated the protective effects of PTX on experimentally induced hepatic toxicity. Hepatic injury in the study was induced by using a single dose of D-Gal, which is a hepatotoxicant, and inducer in hepatic injury models, both in vivo and in vitro. In vivo, D-Gal has been reported to cause hepatic damage resembling viral hepatitis and drug induced hepatitis.<a class="elsevierStyleCrossRef" href="#bib0065">13</a>SYM was used in the present study as a reference and a well-established hepatoprotective agent. This compound has been demonstrated to exhibit hepatoprotectve properties in both in vitro<a class="elsevierStyleCrossRef" href="#bib0070">14</a> and in vivo<a class="elsevierStyleCrossRef" href="#bib0075">15</a> studies. SYM proved to be protective against several hepatotoxicants such as carbon tetrachloride,<a class="elsevierStyleCrossRef" href="#bib0080">16</a> paracetamol,<a class="elsevierStyleCrossRef" href="#bib0085">17</a>,<a class="elsevierStyleCrossRef" href="#bib0090">18</a> and D-Gal<a class="elsevierStyleCrossRef" href="#bib0090">18</a> in different animal models.The current study showed that D-Gal caused a significant decrease in serum albumin level as an indicator of hepatotoxicity, supporting the previous study of Wong, et al.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> Moreover, it is has been shown that the lowering of serum albumin level is attributed to the reduction of albumin mRNA expression, this report observed that there was an abrupt decrease of albumin mRNA which was maximum at the day two after D-Gal administration.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> Noteworthy, the present data showed that pretreatment with PTX significantly inhibited the reduction in serum albumin in D-Gal treated rats compared to control rats. This effect could be explained by ability of PTX to increase the blood flow and irrigation to liver and this might contribute in returning liver vitality. The same effect of PTX on serum albumin level was previously reported.<a class="elsevierStyleCrossRef" href="#bib0105">21</a>On the other hand, D-Gal caused an increase in serum ALP compared to non-treated control group. This rise in serum ALP activity may be attributed to the disturbance in the secretory activity or in the transport of metabolites or may be due to altered synthesis of certain enzymes as in other hepatotoxic conditions.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> The present finding is in accordance with the result of a previous report of Abdel Salam, et al.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> demonstrating an increase of ALP activity in carbon tetrachloride and acetaminophen models of liver injury Serum ALP activity in PTX pretreated group was returned to approximately its normal level compared to D-Gal treated group. This effect, also, was comparable to the effect of SYM on ALP activity in serum, in accordance to the study reported by Peterson.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> We suggest that the bile duct-obstruction may cause more pronounced elevation in ALP activity as ALP is mainly produced in bile duct and its release is enhanced by cholestasis. Thus, PTX failed in preventing that effect.In the current work, administration of single dose of D-Gal caused non significant decrease in triglycerides concentration in the liver, this effect may be due to impairment of hepatic synthesis of triglycerides. Kattermann and Sirowej demonstrated that such decrease could be attributed to sex differences in the fatty liver induced by D-Gal, and the level of hepatic triglycerides content decreased especially in male animals rather than females.Oxidative stress and lipid peroxidation that are mediated by oxygen free radicals has been implicated as a common link between chronic liver damage and hepatic fibrosis.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> Hepatocytes are well recognized as being continuously exposed to reactive oxygen species in various liver diseases including cholestasis. Antioxidant molecules such as glutathione (GSH) and antioxidative enzymes such SOD, and CAT ordinarily provide hepatocytes with resistance to oxidative stresses.<a class="elsevierStyleCrossRef" href="#bib0130">26</a>,<a class="elsevierStyleCrossRef" href="#bib0135">27</a> The reduction of oxidative stress by PTX might be important because increased oxidative stress is a feature of the CCl4-induced liver injury and significant protection was obtained with the use of antioxidants.<a class="elsevierStyleCrossRef" href="#bib0140">28</a>Notably, our study revealed that the single intraperitoneal administration of D-Gal resulted in a significant reduction of tissue catalase and superoxide dismutase activity in addition to elevated level of thiobarbituric acid reactive species (TBARs) as a biochemical marker of lipid peroxidation. It has been suggested that oxygen derived free radicals released from activated hepatic macrophages are the primary cause of D-Gal induced liver damage.<a class="elsevierStyleCrossRef" href="#bib0145">29</a>,<a class="elsevierStyleCrossRef" href="#bib0150">30</a> However, Wong, et al.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> reported an increase in SOD activity which contradicts the present results. They speculated that the upregulation of SOD activity may be attributed to adaptive mechanisms to counteract increased oxidative stress.There are several studies reporting the relevance of CAT to hepatic fibrosis i.e. CAT blocked Tumor Growth Factor B1 (TGF-B1) and collagen production in hepatic stellate cells.<a class="elsevierStyleCrossRef" href="#bib0155">31</a> CAT activity was reduced in human hepatic injury and cirrhosis<a class="elsevierStyleCrossRef" href="#bib0160">32</a> and overexpression of CAT rescued hepatic damage<a class="elsevierStyleCrossRef" href="#bib0165">33</a>. A possible explanation of the effect of D-Gal on CAT activity is the assumption that the impairment of CAT activity might be the cause rather than a consequence of D-Gal hepatotoxicity. Thus, the increase in oxidative stress caused by impaired CAT activity is likely a key element of triggering hepatic fibrosis. This is in agreement with the reported effect of thioacetamide (another hepatotoxic agent) on catalase activity.<a class="elsevierStyleCrossRef" href="#bib0170">34</a> The reduction of CAT activity observed in D-Gal treated group in the study was, also, reported in pervious studies.<a class="elsevierStyleCrossRefs" href="#bib0175">35</a>-<a class="elsevierStyleCrossRef" href="#bib0185">37</a> Pretreatment with PTX prevented D-Gal induced reduction of antioxidative enzymes, SOD and CAT and attenuated the elevated MDA level in hepatic tissue, which observed in control group. This effect may be due to increased blood flow to liver which increases its antioxidant capacity in addition of direct antioxidant effect of PTX and its metabolites. As SYM has strong antioxidative properties and is able to scavenge both free radicals and reactive oxygen species, so it exhibited the same results observed with PTX pretreated group.There is good evidence that cyclic nucleotides are able to prevent oxidative stress by reduction of lipid peroxidation.<a class="elsevierStyleCrossRef" href="#bib0190">38</a> Demir and Inal-Erden<a class="elsevierStyleCrossRef" href="#bib0195">39</a> explained the effects of PTX on production of free radicals to be linked with leukocyte-driven radicals. PTX can enhance the chemotactic response of neutrophils. PTX, also, may inhibit the phagocytosis and superoxide production by neutrophils and monocytes. Savas, et al.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> reported that PTX reduced levels of MDA as well as SOD and CAT activities in a rabbit model of ischemia-reperfusion injury, they attributed these effects to their assumption that PTX is a free radical scavenger and neutrophils stabilizer. Thus, PTX decreases free radical production, antioxidant enzymes and cytokines released from the activated neutrophils. Collectively, these reports support the hypothsis that PTX might exert its hepatotprotective effects due its antioxidant properties.Nitric oxide plays a role in pro-inflammatory cell signaling, altering cellular gene expression, enzyme activity and transcription factor activity. In addition, NO regulates vasodilatation, platelets and neutrophils aggregation, and local organ blood flow. Therefore, NO influences cell and tissue function. The present study revealed that D-Gal induced hepatic injury was associated with elevated NO level. On the other hand, it has been shown that administration of NO donors provides cytoprotection from inflammatory liver damage and hepatocellular apoptosis.<a class="elsevierStyleCrossRef" href="#bib0205">41</a> However, pharmacological blockade of iNOS either aggravates or attenuates liver injury or is ineffective.<a class="elsevierStyleCrossRef" href="#bib0210">42</a> Interestingly, the present results showed that PTX as well as SYM reduced the total level of nitrate/nitrite (the stable metabolite of NO). Such reduction was significant compared to results of non pretreated D-Gal group.Histological changes, especially acute inflammatory response was visible throughout many lobules. The present data suggest that PTX produced protective effects against the disturbed biochemical markers and histopathological findings of D-Gal induced hepatotoxicity in rat model. PTX reduced the levels of toxic free radical and attenuated NO production Thus, PTX increases hepatic antioxidant enzyme activities, and its antioxidant effect appears to play a key role in the attenuation of inflammation. The present results may indicate that PTX and SYM have an antioxidant effect on the increase of the SOD and CAT activities. The combination of PTX with SYM might not provide additional benefits when compared to the use of PTX or SYM alone in the maintenance of antioxidant defense of liver tissues.In conclusion, these results indicate that PTX attenuated the hepatic damage-induced by D-Gal by reducing oxidative stress and increasing the antioxidant defense activities.AcknowledgmentWe thanks Prof. Mohamed Hamid, Vet Medicine, Zagaig University, for his kind help in histopathology study." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres1217517" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abs0010" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1132898" "titulo" => "Key words" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Animals" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Experimental procedures" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Histopathological examination" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 4 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Effects of PTX on the serum albumin and ALP levels" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Effect of PTX on the hepatic oxidative stress markers" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Effect of PTX on the hepatic lipid peroxidation and total nitrite levels" ] 3 => array:2 [ "identificador" => "sec0055" "titulo" => "Histopathological examination" ] ] ] 5 => array:2 [ "identificador" => "sec0060" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0065" "titulo" => "Acknowledgment" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2009-10-22" "fechaAceptado" => "2009-11-13" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec1132898" "palabras" => array:4 [ 0 => "D-galactosamine" 1 => "Hepatotoxicty" 2 => "Pentoxifylline" 3 => "Antioxidant" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "The present study was conducted to investigate effect of pentoxifylline (PTX) on acute liver injury caused by galactosamine (D-Gal) in rats and the underlying mechanism involved in this setting. Moreover, we attempted to compare its effect to the well-established hepatoprotective agent, silymarin (SYM). The rats were randomly assigned 5 groups, control, PTX-treated (100 mg/kg, 3 weeks), SYM-treated (100 mg/kg, 3 weeks) and their combination. Hepatic injury was induced by intraperitoneal single dose injection of D-Gal (800 mg/kg). Hepatic functions parameters, including serum albumin and alkaline phosphatase (ALP) levels were determined. Antioxidants enzyme activities such as superoxide dismutase (SOD), catalase (CAT) as well as lipid peroxides and hepatic total nitrites were measured. Besides, histopathological examination was also performed using portions of liver tissues. Results showed that the liver injury induced by D-Gal was improved in the three pretreated groups to variable extents. Pretreatment with PTX prevented D-Gal-induced reduction of antioxidante enzyme activities, SOD and CAT, and attenuated the elevated malonaldahyde (MDA) level in hepatic tissue as marker of lipid peroxidation. In addition, pretreatment with PTX resulted in an increase in hepatic triglycerides, normalization of nitric oxide level, and lowering serum ALP activity as well as inhibited the decreased serum albumin level caused by D-Gal. These biochemical changes were reflected on attenuation the structural alterations of the liver integrity. Collectively, our data suggest that PTX exhibits a potential hepatoprotective effect against D-Gal-induced hepatotoxicity and this effect might be attributed to its antioxidant properties." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 740 "Ancho" => 2078 "Tamanyo" => 249191 ] ] "descripcion" => array:1 [ "en" => "Effect of D-Gal on the serum albumin and alkaline phosphatase levels in normal rats and rats pretreated with PTX, SYM and their combination. A. Effect of D-Gal on the serum albumin level in normal rats and rats pretreated with PTX, SYM and their combination. B. Effect of D-Gal on the serum alkaline phosphatase in normal rats pretreated with either PTX or SYM or their concurrent administration. Values of each bar represent the mean ± SEM of 7 observations. *Statistically significant of D-Gal-treated group from control group at the significance level p < 0.05. #, f, δ Statistically significant of PTX, SYM and (PTX and SYM) versus D-Gal-treated group, respectively, at the significance level p < 0.05. D-Gal: D-Galactosamine. PTX: Pentoxifylline. SYM: Silymarin." ] ] 1 => array:7 [ "identificador" => "f0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 740 "Ancho" => 2077 "Tamanyo" => 247854 ] ] "descripcion" => array:1 [ "en" => "Effect of D-Gal on antioxidant enzyme activates of liver tissue in normal rats and those pretreated with PTX, SYM and their combination. A. Effect of D-Gal on CAT of liver tissue in normal rats and those pretreated with either PTX or SYM or their combination. B. Effect of D-Gal on CAT of liver tissue in normal rats pretreated with PTX, SYM individually or in combined administration. Values of each bar represent the mean ± SEM of 6 observations. * Statistically significant of D-Gal-treated group from the control group at the significance level p < 0.05. #, f, δ Statistically significant of PTX, SYM and (PTX and SYM) versus D-Gal-treated group, respectively, at the significance level p < 0.05. CAT: Catalase. SOD: Superoxide dismutase and other symbols as in <a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>." ] ] 2 => array:7 [ "identificador" => "f0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 744 "Ancho" => 2077 "Tamanyo" => 226078 ] ] "descripcion" => array:1 [ "en" => "Effect of D-Gal on hepatic lipid peroxidation and total nitrites in normal rats and those pretreated with PTX, SYM and their combination. A. Effect of D-Gal on the hepatic lipid peroxidation in normal rats pretreated with either PTX or SYM or their combination. B. Effect of D-Gal on the hepatic total nitrites in normal rats pretreated with PTX and SYM individually or in concurrent administration. Values of each bar represent the mean ± SEM of 7 observations. * Statistically significant from the control group at the significance level p < 0.05. #, f, δ Statistically significant of PTX, SYM and (PTX and SYM) versus D-Gal-treated group, respectively, at the significance level p < 0.05. MDA: Malondialdhyde and other symbols as in <a class="elsevierStyleCrossRef" href="#f0005">Figure 1</a>." ] ] 3 => array:7 [ "identificador" => "f0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 967 "Ancho" => 1507 "Tamanyo" => 357318 ] ] "descripcion" => array:1 [ "en" => "Histopathological analysis to the effects D-Gal on liver in the absence or present of either PTX or SYM. (A) Liver of the control group illustrates normal parenchymal and sinusoidal structures, H&E. (B) Liver of D-Gal-treated group showing portal area with thickening and hyalinization of the tunica media of hepatic arteriole (arrow), H&E. x 500. (C) Liver PTX-treated group reveals portal area with congested blood vessel (arrow head) and few round cell infiltrations (arrow), HE x 300. (D) liver of SYM-treated group shows portal area with few round cell infiltrations (arrow head), HE x 300." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:42 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Teas and other beverages suppress D-galactosamine-induced liver injury in rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Sugiyama K." 1 => "He P." 2 => "Wada S." 3 => "Saeki S." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Xutr" "fecha" => "1999" "volumen" => "129" "numero" => "7" "paginaInicial" => "1361" "paginaFinal" => "1367" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protective effect of Lygodium flexuosum (L.) Sw. (Lygodiaceae) against D-galactosamine induced liver injury in rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Wills P.J." 1 => "Asha VV." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jep.2006.04.028" "Revista" => array:7 [ "tituloSerie" => "J Ethnopharmacol" "fecha" => "2006" "volumen" => "108" "numero" => "1" "paginaInicial" => "116" "paginaFinal" => "123" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16797898" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunohistochemical study of extracellular matrix in acute galactosamine hepatitis in rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Jonker A.M." 1 => "Dijkhuis F.W." 2 => "Boes A." 3 => "Hardonk M.J." 4 => "Grond J." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Hepatology" "fecha" => "1992" "volumen" => "15" "numero" => "3" "paginaInicial" => "423" "paginaFinal" => "431" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1371983" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Selective uridine triphosphate deficiency induced by D-galactosamine in liver and reversed by pyrimidine nucleotide precursors. Effect on ribonucleic acid synthesis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Keppler D.O." 1 => "Pausch J." 2 => "Decker K." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Biol Chem" "fecha" => "1974" "volumen" => "249" "numero" => "1" "paginaInicial" => "211" "paginaFinal" => "216" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4809627" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protection by phosphodiesterase inhibitors against endotoxin-induced liver injury in galactosamine-sensitized mice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Fischer W." 1 => "Schudt C." 2 => "Wendel A." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/0006-2952(93)90219-m" "Revista" => array:7 [ "tituloSerie" => "Biochem Pharmacol" "fecha" => "1993" "volumen" => "45" "numero" => "12" "paginaInicial" => "2399" "paginaFinal" => "2404" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8392340" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protection by a cyclic AMP-specific phosphodiesterase inhibitor, rolipram, and dibutyryl cyclic AMP against Propionibacterium acnes and lipopolysaccharide-induced mouse hepatitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Taguchi I." 1 => "Oka K." 2 => "Kitamura K." 3 => "Sugiura M." 4 => "Oku A." 5 => "Matsumoto M." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s000110050475" "Revista" => array:7 [ "tituloSerie" => "Inflamm Res" "fecha" => "1999" "volumen" => "48" "numero" => "7" "paginaInicial" => "380" "paginaFinal" => "385" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10450787" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effects of pentoxifylline on spinal cord blood flow after experimental spinal cord injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Thompson M.K." 1 => "Tuma R.F." 2 => "Young WF." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Assoc Acad Minor Phys" "fecha" => "1999" "volumen" => "10" "numero" => "1" "paginaInicial" => "23" "paginaFinal" => "26" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10826005" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "In vivo effect of free radical scavenger hepatoprotective agents on superoxide dismutase (SOD) activity in patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Feher J." 1 => "Lang I." 2 => "Nekam K." 3 => "Gergely P." 4 => "Muzes G." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Tokai J Exp Clin Med" "fecha" => "1990" "volumen" => "15" "numero" => "2-3" "paginaInicial" => "129" "paginaFinal" => "134" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2130521" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Silybin inhibition of amatoxin uptake in the perfused rat liver" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Faulstich H." 1 => "Jahn W." 2 => "Wieland T." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Arzneimittelforschung" "fecha" => "1980" "volumen" => "30" "numero" => "3" "paginaInicial" => "452" "paginaFinal" => "454" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7387753" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The anti-inflammatory effects of the phosphodiesterase inhibitor pentoxifylline in the rat" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Abdel-Salam O.M." 1 => "Baiuomy A.R." 2 => "El-Shenawy S.M." 3 => "Arbid MS." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Pharmacol Res" "fecha" => "2003" "volumen" => "47" "numero" => "4" "paginaInicial" => "331" "paginaFinal" => "340" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12644391" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Microsomal lipid peroxidation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Buege J.A." 1 => "Aust SD." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Methods Enzymol" "fecha" => "1978" "volumen" => "52" "paginaInicial" => "302" "paginaFinal" => "310" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/672633" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lipid peroxide and reactive oxygen species generating systems of the crystalline lens" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Babizhayev M.A." 1 => "Costa EB." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/0925-4439(94)90014-0" "Revista" => array:7 [ "tituloSerie" => "Biochimica et biophysica acta" "fecha" => "1994" "volumen" => "1225" "numero" => "3" "paginaInicial" => "326" "paginaFinal" => "337" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8312381" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pectolinarin and Pectolinarigenin of Cirsium setidens Prevent the Hepatic Injury in Rats Caused by D-Galactosamine via an Antioxidant Mechanism" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Yoo Y.M." 1 => "Nam J.H." 2 => "Kim M.Y." 3 => "Choi J." 4 => "Park HJ." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Biol Pharm Bull" "fecha" => "2008" "volumen" => "31" "numero" => "4" "paginaInicial" => "760" "paginaFinal" => "764" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18379079" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biochemical effects of the flavonolignane silibinin on RNA, protein and DNA synthesis in rat livers" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Sonnenbichler J." 1 => "Zetl I." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Prog Clin Biol Res" "fecha" => "1986" "volumen" => "213" "paginaInicial" => "319" "paginaFinal" => "331" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2424029" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protective and therapeutic effect of silymarin on the development of latent liver damage" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Kropacova K." 1 => "Misurova E." 2 => "Hakova H." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Radiats Biol Radioecol" "fecha" => "1998" "volumen" => "38" "numero" => "3" "paginaInicial" => "411" "paginaFinal" => "415" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9682736" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevention by silymarin of membrane alterations in acute CCl4 liver damage" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Muriel P." 1 => "Mourelle M." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Appl Toxicol" "fecha" => "1990" "volumen" => "10" "numero" => "4" "paginaInicial" => "275" "paginaFinal" => "279" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1975258" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Silymarin mediated differential modulation of toxicity induced by carbon tetrachloride, paracetamol and D-galactosamine in freshly isolated rat hepatocytes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Chrungoo V.J." 1 => "Singh K." 2 => "Singh J." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Indian J Exp Biol" "fecha" => "1997" "volumen" => "35" "numero" => "6" "paginaInicial" => "611" "paginaFinal" => "617" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9357165" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protective activity of silipide on liver damage in rodents" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Conti M." 1 => "Malandrino S." 2 => "Magistretti MJ." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Jpn J Pharmacol" "fecha" => "1992" "volumen" => "60" "numero" => "4" "paginaInicial" => "315" "paginaFinal" => "320" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1287266" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The cytoprotective effect of alpha-tocopherol and daidzein against d-galactosamine-induced oxidative damage in the rat liver" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:5 [ 0 => "Wong M.C." 1 => "Portmann B." 2 => "Sherwood R." 3 => "Niemela O." 4 => "Koivisto H." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.metabol.2007.01.005" "Revista" => array:8 [ "tituloSerie" => "Metabolism" "fecha" => "2007" "volumen" => "56" "numero" => "7" "paginaInicial" => "865" "paginaFinal" => "875" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17570244" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673615010375" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Activation, proliferation, and differentiation of progenitor cells into hepatocytes in the D-galactosamine model of liver regeneration" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Dabeva M.D." 1 => "Shafritz DA." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Am J Pathol" "fecha" => "1993" "volumen" => "143" "numero" => "6" "paginaInicial" => "1606" "paginaFinal" => "1620" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7504886" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pentoxifylline prevents fibrosis in an animal model and inhibits platelet-derived growth factor-driven proliferation of fibroblasts" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Peterson TC." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Hepatology" "fecha" => "1993" "volumen" => "17" "numero" => "3" "paginaInicial" => "486" "paginaFinal" => "493" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8095247" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nature of inhibition of rat testicular alkaline phosphatase by isatin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Kumar P." 1 => "Nagpaul J.P." 2 => "Singh B." 3 => "Bansal R.C." 4 => "Sharma R." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/bf01935909" "Revista" => array:7 [ "tituloSerie" => "Experientia" "fecha" => "1978" "volumen" => "34" "numero" => "4" "paginaInicial" => "434" "paginaFinal" => "435" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/639934" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of pentoxifylline on hepatic injury caused in the rat by the administration of carbon tetrachloride or acetaminophen." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Abdel S.O.M." 1 => "Baiuomy A.R." 2 => "El-Shenawy S.M." 3 => "Hassan NS." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Pharmacol Rep" "fecha" => "Sep-Oct 2005" "volumen" => "57" "numero" => "5" "paginaInicial" => "596" "paginaFinal" => "603" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16227642" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Liver injury and lipid metabolism: sex differences in the fatty liver induced by d-galactosamine" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Kattermann R." 1 => "Sirowej H." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Acta Hepatogastroenterol (Stuttg)" "fecha" => "1979" "volumen" => "2" "numero" => "26" "paginaInicial" => "112" "paginaFinal" => "126" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatoprotective and antifibrotic effect of a new silybin-phosphatidylcholine-Vitamin E complex in rats" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Di Sario A." 1 => "Bendia E." 2 => "Taffetani S." 3 => "Omenetti A." 4 => "Candelaresi C." 5 => "Marzioni M." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.dld.2005.05.011" "Revista" => array:7 [ "tituloSerie" => "Dig Liver Dis" "fecha" => "2005" "volumen" => "37" "numero" => "11" "paginaInicial" => "869" "paginaFinal" => "876" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16169303" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Role of ursodeoxycholic acid in prevention of hepatotoxicity caused by amoxicillin-clavulanic acid in rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "El-Sherbiny G.A." 1 => "Taye A." 2 => "Abdel-Raheem IT." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Ann Hepatol" "fecha" => "2009" "volumen" => "8" "numero" => "2" "paginaInicial" => "134" "paginaFinal" => "140" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19502657" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Responses of antioxidant systems in the hepatocytes of common carp (Cyprinus carpio L.) to the toxicity of microcystin-LR" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Li X." 1 => "Liu Y." 2 => "Song L." 3 => "Liu J." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Toxicon" "fecha" => "2003" "volumen" => "42" "numero" => "1" "paginaInicial" => "85" "paginaFinal" => "89" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12893065" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo: the protective effect of allopurinol" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Jaeschke H." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Pharmacol Exp Ther" "fecha" => "1990" "volumen" => "255" "numero" => "3" "paginaInicial" => "935" "paginaFinal" => "941" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2262912" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Modulation of hepatotoxicity by macrophages in the liver" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Shiratori Y." 1 => "Kawase T." 2 => "Shiina S." 3 => "Okano K." 4 => "Sugimoto T." 5 => "Teraoka H." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Hepatology" "fecha" => "1988" "volumen" => "8" "numero" => "4" "paginaInicial" => "815" "paginaFinal" => "821" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2839405" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changes in free radicals, trace elements, and neurophysiological function in rats with liver damage induced by D-galactosamine" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Hu H.L." 1 => "Chen RD." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/BF02783894" "Revista" => array:7 [ "tituloSerie" => "Biol Trace Elem Res" "fecha" => "1992" "volumen" => "34" "numero" => "1" "paginaInicial" => "19" "paginaFinal" => "25" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1382518" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glutathione levels discriminate between oxidative stress and transforming growth factor-beta signaling in activated rat hepatic stellate cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "De Bleser P.J." 1 => "Xu G." 2 => "Rombouts K." 3 => "Rogiers V." 4 => "Geerts A." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1074/jbc.274.48.33881" "Revista" => array:7 [ "tituloSerie" => "J Biol Chem" "fecha" => "1999" "volumen" => "274" "numero" => "48" "paginaInicial" => "33881" "paginaFinal" => "33887" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10567349" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antioxidant enzyme status in biliary obstructed rats: effects of N-acetylcysteine" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Pastor A." 1 => "Collado P.S." 2 => "Almar M." 3 => "Gonzalez-Gallego J." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Hepatol" "fecha" => "1997" "volumen" => "27" "numero" => "2" "paginaInicial" => "363" "paginaFinal" => "370" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9288612" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adenovirus-mediated overexpression of catalase in the cytosolic or mitochondrial compartment protects against cytochrome P450 2E1-dependent toxicity in HepG2 cells" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Bai J." 1 => "Cederbaum Al." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1074/jbc.M008895200" "Revista" => array:7 [ "tituloSerie" => "J Biol Chem" "fecha" => "2001" "volumen" => "276" "numero" => "6" "paginaInicial" => "4315" "paginaFinal" => "4321" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11071897" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PPARalpha ligands activate antioxidant enzymes and suppress hepatic fibrosis in rats" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Toyama T." 1 => "Nakamura H." 2 => "Harano Y." 3 => "Yamauchi N." 4 => "Morita A." 5 => "Kirishima T." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbrc.2004.09.110" "Revista" => array:8 [ "tituloSerie" => "Biochem Biophys Res Commun" "fecha" => "2004" "volumen" => "324" "numero" => "2" "paginaInicial" => "697" "paginaFinal" => "704" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15474484" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1470204512703790" "estado" => "S300" "issn" => "14702045" ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatoprotective effect of Picrorrhiza kurroa on tissue defence system in-galactosamine-induced hepatitis in rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Anandan R." 1 => "Devaki T." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Fitoterapia" "fecha" => "1999" "volumen" => "70" "numero" => "1" "paginaInicial" => "54" "paginaFinal" => "57" ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antihepatotoxic potential of Sargassum polycystum (Phaeophyceae) on antioxidant defense status in Dgalactosamine-induced hepatitis in rats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Meena B." 1 => "Anbin E.R." 2 => "Rajesh R." 3 => "Sheik H.A." 4 => "Ganesan B." 5 => "Anandan R." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Afr J Biochem Res" "fecha" => "2008" "volumen" => "2" "numero" => "2" "paginaInicial" => "51" "paginaFinal" => "55" ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hepatoprotective effect of allicin on tissue defense system in galactosamine/endotoxin challenged rats." "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Vimal V." 1 => "Devaki T." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:8 [ "tituloSerie" => "J Ethnopharmacol" "fecha" => "2004" "volumen" => "90" "numero" => "1" "paginaInicial" => "151" "paginaFinal" => "154" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14698523" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0090429516305519" "estado" => "S300" "issn" => "00904295" ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protection by sildenafil and theophylline of lead acetate-induced oxidative stress in rat submandibular gland and saliva" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Abdollahi M." 1 => "Fooladian F." 2 => "Emami B." 3 => "Zafari K." 4 => "Bahreini-Moghadam A." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1191/0960327103ht399oa" "Revista" => array:7 [ "tituloSerie" => "Hum Exp Toxicol" "fecha" => "2003" "volumen" => "22" "numero" => "11" "paginaInicial" => "587" "paginaFinal" => "592" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14686481" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pentoxifylline and N-acetylcysteine in hepatic ischemia/reperfusion injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Demir S." 1 => "lnal-Erden M." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Clin Chim Acta" "fecha" => "1998" "volumen" => "275" "numero" => "2" "paginaInicial" => "127" "paginaFinal" => "135" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9721071" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pentoxifylline reduces biochemical markers of ischemia-reperfusion induced spinal cord injury in rabbits" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Savas S." 1 => "Delibas N." 2 => "Savas C." 3 => "Sutcu R." 4 => "Cindas A." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.sc.3101281" "Revista" => array:7 [ "tituloSerie" => "Spinal Cord" "fecha" => "2002" "volumen" => "40" "numero" => "5" "paginaInicial" => "224" "paginaFinal" => "229" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11987004" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inducible nitric oxide synthase is critical for immune-mediated liver injury in mice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Sass G." 1 => "Koerber K." 2 => "Bang R." 3 => "Guehring H." 4 => "Tiegs G." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI10613" "Revista" => array:7 [ "tituloSerie" => "J Clin Invest" "fecha" => "2001" "volumen" => "107" "numero" => "4" "paginaInicial" => "439" "paginaFinal" => "447" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11181643" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Nitric Oxide. IV. Determinants of nitric oxide protection and toxicity in liver" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Li J." 1 => "Billiar TR." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/ajpgi.1999.276.5.G1069" "Revista" => array:7 [ "tituloSerie" => "Am J Physiol" "fecha" => "1999" "volumen" => "276" "numero" => "5 Pt 1" "paginaInicial" => "G1069" "paginaFinal" => "G1073" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10329995" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/16652681/0000000800000004/v1_201907070733/S166526811931751X/v1_201907070733/en/main.assets" "Apartado" => array:4 [ "identificador" => "77721" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/16652681/0000000800000004/v1_201907070733/S166526811931751X/v1_201907070733/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S166526811931751X?idApp=UINPBA00004N"]

Statistics

Ashraf Taye

Corresponding author

Ashraf_taye70@yahoo.com

Correspondence and reprint request:

, Mohamed A. El-Moselhy*, Magdy K.A. Hassan**, Hanaa M. Ibrahim**, Aliaa F. Mohammed*

* Department of Pharmacology & Toxicology, Faculty of Pharmacy, Minia University

** Department of Physiology, Faculty of Medicine, Minia University

Read

1493

Times
was read the article

417

Total PDF

1076

Total HTML

Share statistics

 array:24 [
  "pii" => "S166526811931751X"
  "issn" => "16652681"
  "doi" => "10.1016/S1665-2681(19)31751-X"
  "estado" => "S300"
  "fechaPublicacion" => "2009-10-01"
  "aid" => "71413"
  "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
  "copyrightAnyo" => "2009"
  "documento" => "article"
  "crossmark" => 0
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "fla"
  "cita" => "Ann Hepatol. 2009;8:364-70"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 61
    "formatos" => array:3 [
      "EPUB" => 12
      "HTML" => 28
      "PDF" => 21
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S1665268119317521"
    "issn" => "16652681"
    "doi" => "10.1016/S1665-2681(19)31752-1"
    "estado" => "S300"
    "fechaPublicacion" => "2009-10-01"
    "aid" => "71414"
    "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Ann Hepatol. 2009;8:371-6"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 60
      "formatos" => array:3 [
        "EPUB" => 13
        "HTML" => 21
        "PDF" => 26
      ]
    ]
    "en" => array:11 [
      "idiomaDefecto" => true
      "titulo" => "Acute treatment of constant darkness increases the efficiency of ATP synthase in rat liver mitochondria"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "371"
          "paginaFinal" => "376"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "f0005"
          "etiqueta" => "<span class="elsevierStyleBold"><span class="elsevierStyleItalic">Figure 1</span></span>"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1394
              "Ancho" => 2079
              "Tamanyo" => 332695
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">ATP synthase activity <span class="elsevierStyleBold">&#40;A&#41;</span>&#44; ATPase activity <span class="elsevierStyleBold">&#40;B&#41;</span>&#44; &#37; ACMA fluorescence quenching <span class="elsevierStyleBold">&#40;C&#41;</span> and excimer&#47;monomer intensity fluorescence ratio <span class="elsevierStyleBold">&#40;D&#41;</span> in mitochondria <span class="elsevierStyleBold">&#40;A&#41;</span> and submitochondrial particles <span class="elsevierStyleBold">&#40;B&#44; C&#44; D&#41;</span> from rats kept under constant darkness and normal cycles of light&#47;dark&#46; Enzymatic activities and membrane fluidity determinations were done as described in Methods&#46; The data shown are mean &#177; S&#46;E&#46; &#42;p &#60; 0&#46;05&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Ana Laura Ram&#237;rez-I&#241;iguez, Genaro Gabriel Ortiz, Mohammed El Hafidi, Ana Rosa Rinc&#243;n-S&#225;nchez, Ernesto Mac&#237;as-Rodr&#237;guez, Ferm&#237;n Paul Pacheco-Mois&#233;s"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Ana"
              "apellidos" => "Laura Ram&#237;rez-I&#241;iguez"
            ]
            1 => array:2 [
              "nombre" => "Genaro"
              "apellidos" => "Gabriel Ortiz"
            ]
            2 => array:2 [
              "nombre" => "Mohammed"
              "apellidos" => "El Hafidi"
            ]
            3 => array:2 [
              "nombre" => "Ana"
              "apellidos" => "Rosa Rinc&#243;n-S&#225;nchez"
            ]
            4 => array:2 [
              "nombre" => "Ernesto"
              "apellidos" => "Mac&#237;as-Rodr&#237;guez"
            ]
            5 => array:2 [
              "nombre" => "Ferm&#237;n"
              "apellidos" => "Paul Pacheco-Mois&#233;s"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119317521?idApp=UINPBA00004N"
    "url" => "/16652681/0000000800000004/v1_201907070733/S1665268119317521/v1_201907070733/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S1665268119317508"
    "issn" => "16652681"
    "doi" => "10.1016/S1665-2681(19)31750-8"
    "estado" => "S300"
    "fechaPublicacion" => "2009-10-01"
    "aid" => "71412"
    "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
    "documento" => "article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Ann Hepatol. 2009;8:359-63"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 178
      "formatos" => array:3 [
        "EPUB" => 9
        "HTML" => 140
        "PDF" => 29
      ]
    ]
    "en" => array:10 [
      "idiomaDefecto" => true
      "titulo" => "The safety and feasibility of large volume paracentesis performed by an experienced nurse practitioner"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "359"
          "paginaFinal" => "363"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Nooman Gilani, Nayan Patel, Richard D Gerkin, Francisco C Ramirez, Erin E Tharalson, Kandarp Patel"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Nooman"
              "apellidos" => "Gilani"
            ]
            1 => array:2 [
              "nombre" => "Nayan"
              "apellidos" => "Patel"
            ]
            2 => array:2 [
              "nombre" => "Richard D"
              "apellidos" => "Gerkin"
            ]
            3 => array:2 [
              "nombre" => "Francisco C"
              "apellidos" => "Ramirez"
            ]
            4 => array:2 [
              "nombre" => "Erin E"
              "apellidos" => "Tharalson"
            ]
            5 => array:2 [
              "nombre" => "Kandarp"
              "apellidos" => "Patel"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119317508?idApp=UINPBA00004N"
    "url" => "/16652681/0000000800000004/v1_201907070733/S1665268119317508/v1_201907070733/en/main.assets"
  ]
  "en" => array:17 [
    "idiomaDefecto" => true
    "titulo" => "Hepatoprotective effect of pentoxifylline against D-galactosamine-induced hepatotoxicity in rats"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "364"
        "paginaFinal" => "370"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Ashraf Taye, Mohamed A&#46; El-Moselhy, Magdy K&#46;A&#46; Hassan, Hanaa M&#46; Ibrahim, Aliaa F&#46; Mohammed"
        "autores" => array:5 [
          0 => array:4 [
            "nombre" => "Ashraf"
            "apellidos" => "Taye"
            "email" => array:1 [
              0 => "Ashraf_taye70@yahoo.com"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "aff1"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor1"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Mohamed A&#46;"
            "apellidos" => "El-Moselhy"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "aff1"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Magdy K&#46;A&#46;"
            "apellidos" => "Hassan"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;&#42;</span>"
                "identificador" => "aff2"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Hanaa M&#46;"
            "apellidos" => "Ibrahim"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;&#42;</span>"
                "identificador" => "aff2"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Aliaa F&#46;"
            "apellidos" => "Mohammed"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "aff1"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:2 [
          0 => array:3 [
            "entidad" => "Department of Pharmacology &#38; Toxicology&#44; Faculty of Pharmacy&#44; Minia University"
            "etiqueta" => "&#42;"
            "identificador" => "aff1"
          ]
          1 => array:3 [
            "entidad" => "Department of Physiology&#44; Faculty of Medicine&#44; Minia University"
            "etiqueta" => "&#42;&#42;"
            "identificador" => "aff2"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor1"
            "etiqueta" => "&#42;"
            "correspondencia" => "Correspondence and reprint request&#58;"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "f0015"
        "etiqueta" => "<span class="elsevierStyleBold"><span class="elsevierStyleItalic">Figure 3</span></span>"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 744
            "Ancho" => 2077
            "Tamanyo" => 226078
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Effect of D-Gal on hepatic lipid peroxidation and total nitrites in normal rats and those pretreated with PTX&#44; SYM and their combination&#46; <span class="elsevierStyleBold">A&#46;</span> Effect of D-Gal on the hepatic lipid peroxidation in normal rats pretreated with either PTX or SYM or their combination&#46; <span class="elsevierStyleBold">B&#46;</span> Effect of D-Gal on the hepatic total nitrites in normal rats pretreated with PTX and SYM individually or in concurrent administration&#46; Values of each bar represent the mean &#177; SEM of 7 observations&#46; <span class="elsevierStyleBold">&#42;</span> Statistically significant from the control group at the significance level p &#60; 0&#46;05&#46; &#35;&#44; f&#44; &#948; Statistically significant of PTX&#44; SYM and &#40;PTX and SYM&#41; versus D-Gal-treated group&#44; respectively&#44; at the significance level p &#60; 0&#46;05&#46; <span class="elsevierStyleBold">MDA&#58;</span> Malondialdhyde and other symbols as in <a class="elsevierStyleCrossRef" href="#f0005"><span class="elsevierStyleItalic">Figure 1</span></a>&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="p0005" class="elsevierStylePara elsevierViewall">Liver injury can be caused by different agents&#44; such as viruses&#44; chemicals&#44; alcohol&#44; and auto-immune diseases<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> D-galactosamine &#40;D-Gal&#41; is a well established hepatotoxicant&#44; it induces a diffuse type of liver injury closely resembling human viral hepatitis<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and acute self-limiting hepatitis with necrosis&#44; inflammation and regeneration&#44; resembling a drug-induced disease in humans&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> The toxicity of D-Gal is mainly related to the depletion of uridine pools that are associated with limited ribonucleic acid &#40;RNA&#41; and protein synthesis&#44; thus altering hepatocellular function&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">Different pharmacological compounds have been tested to reduce acute or chronic inflammatory responses&#44; which may damage liver function&#46; It has been demonstrated that phosphodiesterase inhibitors may be protective in various liver injury models&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Pentoxifylline &#40;PTX&#41; &#40;non-selective phosphodiesterase inhibitor&#41; is a methyl xanthine derivative that has been used for its regulatory effect on blood flow&#46; PTX increases the flexibility of red and white blood cells&#44; reduces the blood viscosity by decreasing plasma fibrinogen concentrations and decrease platelet aggregation and thrombus formation&#46; Polymorphonuclear leukocyte-mediated effects&#44; such as superoxide production&#44; chemotaxis&#44; phagocytosis and tumor necrosis factor &#40;TNF&#41; production are inhibited by PTX&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="p0015" class="elsevierStylePara elsevierViewall">Silymarin &#40;SYM&#41; from milk thistle is a hepatoprotective drug was widely used in the world&#46; SYM may reduce free radical production and lipid peroxidation in the setting of hepatotoxicity as it has powerful antioxidant properties&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> SYM may act through its ability for toxin blockade&#59; it may bind to the hepatocyte cell membrane receptor site&#44; inhibiting binding of toxins to these sites&#46;</p><p id="p0020" class="elsevierStylePara elsevierViewall">The aim of the present study was to examine the putative hepatoprotective effects of PTX against hepatotoxicity induced by D-Gal and elucidate the underlying mechanisms involved in this protection&#44; as a sole effect or synergistic with SYM&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Material and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Animals</span><p id="p0025" class="elsevierStylePara elsevierViewall">Animals used in the present study were male albino rats &#40;8 weeks of age&#41; weighing 180-200 g&#46; Animals were kept under constant environmental conditions throughout the period of the experiment&#46; Animals were exposed to dark&#47;light cycle of 12&#58;12 hours&#46; Experiments were conducted in accordance with the guidelines for animal care of the United States Naval Medical Research Centre&#44; Unit No&#46; 3&#44; Abbaseya&#44; Cairo&#44; Egypt&#44; accredited by the Association for Assessment and Accreditation of Laboratory Animal Care international &#40;AAALAC international&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Experimental procedures</span><p id="p0030" class="elsevierStylePara elsevierViewall">All animals were fed standard animal chow along the period of the experiment &#40;21 days&#41;&#46; After the acclimatization period&#44; the rats were divided into five groups&#44; each of 12 rats&#46; Firstly&#44; control group&#59; in which animals received saline 0&#46;5 mL&#47;day i&#46;p&#46; for 3 weeks&#46; Second&#44; D-GAL-treated group&#59; in which animals received saline 0&#46;5 mL&#47;day i&#46;p&#46; for 3 weeks and at 21<span class="elsevierStyleSup">st</span> day received a single dose of D-GAL&#46; Third&#44; PTX-treated group&#59; animals received PTX &#40;100 mg&#47;kg&#47;day&#44; i&#46;p&#46;&#41; dissolved in 0&#46;5 mL saline for 3 weeks&#46; Fourth&#44; SYM-treated group&#59; in which animals received SYM &#40;100 mg&#47;kg&#47;day&#44; oral&#41; suspended in 0&#46;5 mL 0&#46;1&#37; starch solution for 3 weeks&#46; Fifth&#44; PTX &#43; SYL group&#59; animals received PTX followed by simultaneous administration of SYM for 3 weeks by the same previous doses as previously described&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="p0035" class="elsevierStylePara elsevierViewall">All groups except group 1 received at 21<span class="elsevierStyleSup">st</span> day a single dose of D-Gal &#40;800 mg&#47;kg&#44; i&#46;p&#46;&#41; once in the morning&#46; At the end of the study&#44; the animals were sacrificed and blood was collected for separation of sera&#46; The livers were isolated&#44; washed off blood and connective tissue was removed then portions of liver tissues were separated and kept in 10&#37; formalin for histopathological examination&#46;</p><p id="p0040" class="elsevierStylePara elsevierViewall">Immediately&#44; the rest of liver tissues were immediately flash-frozen in liquid nitrogen and stored at - 80 &#176;C&#46; Kits used for determination of malonaldahyde &#40;MDA&#41; levels &#40;Biodiagnostic&#44; Egypt&#41; as a marker of lipid peroxides&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> tissue nitrite as an indicator of nitric oxide &#40;Biodiagnostic&#44; Egypt&#41;&#44; albumin &#40;DP International&#44; Egypt&#41;&#44; alkaline phosphatase &#40;ALP&#41;&#44; and total protein concentrations &#40;Spectrum Diagnostics&#44; Egypt&#41;&#44; superoxide dismutase &#40;SOD&#41; and catalase &#40;CAT&#41; enzymes<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> &#40;Biodiagnostic&#44; Egypt&#41;&#46; In addition&#44; serum albumin levels and ALP activities were measured in sera of all the experimental animals&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Histopathological examination</span><p id="p0045" class="elsevierStylePara elsevierViewall">Small pieces of the livers fixed in 10&#37; buffered neutral formalin were processed for embedding in paraffin&#46; Sections of 5-6 mm thickness were stained with hematoxylin and eosin&#44; examined for histopathological changes&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Statistical analysis</span><p id="p0050" class="elsevierStylePara elsevierViewall">Results were expressed as means &#177; standard error of the mean &#40;SEM&#41; and were analyzed for statistically significant difference using one-way analysis of variance &#40;ANOVA&#41; followed by the Tukey-Kramar post analysis test&#46; P values less than 0&#46;05 were considered significant&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Effects of PTX on the serum albumin and ALP levels</span><p id="p0055" class="elsevierStylePara elsevierViewall">D-Gal exhibited a significant reduction of serum albumin level when compared to control rats&#46; However&#44; the individual or combined administration of either PTX or SYM resulted in a significant elevation in serum albumin level nearly to the control level &#40;<a class="elsevierStyleCrossRef" href="#f0005">Figure 1A</a>&#41;&#46; Administration of D-Gal resulted in a significant elevation of serum ALP activity in comparison to the control rats&#46; Meanwhile&#44; the single or combined administration of either PTX or SYM exerted a marked reduction in the serum ALP activity to the normal level &#40;<a class="elsevierStyleCrossRef" href="#f0005">Figure 1B</a>&#41;&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Effect of PTX on the hepatic oxidative stress markers</span><p id="p0060" class="elsevierStylePara elsevierViewall">D-Gal produced a significant decrease of CAT activity when compared to control rats&#46; Pretreatment with either PTX or SYM significantly increased CAT activity of liver tissue compared to D-Gal-treated group&#46; Combined administration of PTX and SYM significantly increased the hepatic CAT activity compared to D-Gal-treated group &#40;<a class="elsevierStyleCrossRef" href="#f0010">Figure 2A</a>&#41;&#46; The activity of SOD was significantly reduced in D-Gal group as compared to control rats&#46; In PTX pretreated group&#44; a significant increase of SOD activity was observed compared to D-Gal-treated group&#46; Meanwhile&#44; pretreatment with SYM or &#40;PTX &#43; SYM&#41; significantly increased SOD activity when compared to D-Gal-treated group &#40;<a class="elsevierStyleCrossRef" href="#f0010">Figure 2B</a>&#41;&#46;</p><elsevierMultimedia ident="f0010"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Effect of PTX on the hepatic lipid peroxidation and total nitrite levels</span><p id="p0065" class="elsevierStylePara elsevierViewall">Intraperitoneal administration of D-Gal significantly elevated the hepatic tissue MDA concentration &#40;a biochemical marker of lipid peroxidation&#41; to about two-fold of the value observed in control group &#40;<a class="elsevierStyleCrossRef" href="#f0015">Figure 3A</a>&#41;&#46;</p><elsevierMultimedia ident="f0015"></elsevierMultimedia><p id="p0070" class="elsevierStylePara elsevierViewall">On the other hand&#44; the total hepatic nitrite level was significantly elevated in D-Gal treated groups compared to the control group&#46; However&#44; the single or combined administration of PTX and SYM significantly restored the elevated hepatic total nitrites to the normal level &#40;<a class="elsevierStyleCrossRef" href="#f0015">Figure 3B</a>&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Histopathological examination</span><p id="p0075" class="elsevierStylePara elsevierViewall">To verify the biochemical changes in liver&#44; the histopathological examination of liver both of the control and treated rats was performed&#46; The liver of the control group was normal with no evidence of any microscopic abnormalities &#40;<a class="elsevierStyleCrossRef" href="#f0020">Figure 4A</a>&#41;&#46; In D-Gal-treated group&#44; microscopically&#44; vasculitis&#44; represented by congested blood vessels and perivascular edema and few lymphocytes infiltrations was noticed&#46; Thickening and hyalinization of the tunica media of hepatic arterioles were observed &#40;<a class="elsevierStyleCrossRef" href="#f0020">Figure 4B</a>&#41;&#46; In PTX group&#44; microscopically&#44; some portal areas showed congested blood vessels and leukocyte margination and emigration besides mild hyperplasia of the epithelial lining of the bile ducts and few round cell infiltrations &#40;<a class="elsevierStyleCrossRef" href="#f0015">Figure 4C</a>&#41;&#46; In SYM-treated group&#44; few round cells &#40;mainly of lymphocytes&#41; in the portal areas and the interstitial tissue were detected &#40;<a class="elsevierStyleCrossRef" href="#f0020">Figure 4D</a>&#41;&#46;</p><elsevierMultimedia ident="f0020"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Discussion</span><p id="p0080" class="elsevierStylePara elsevierViewall">The current study investigated the protective effects of PTX on experimentally induced hepatic toxicity&#46; Hepatic injury in the study was induced by using a single dose of D-Gal&#44; which is a hepatotoxicant&#44; and inducer in hepatic injury models&#44; both <span class="elsevierStyleItalic">in vivo</span> and <span class="elsevierStyleItalic">in vitro</span>&#46; <span class="elsevierStyleItalic">In vivo</span>&#44; D-Gal has been reported to cause hepatic damage resembling viral hepatitis and drug induced hepatitis&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="p0085" class="elsevierStylePara elsevierViewall">SYM was used in the present study as a reference and a well-established hepatoprotective agent&#46; This compound has been demonstrated to exhibit hepatoprotectve properties in both <span class="elsevierStyleItalic">in vitro</span><a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> and <span class="elsevierStyleItalic">in vivo</span><a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> studies&#46; SYM proved to be protective against several hepatotoxicants such as carbon tetrachloride&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> paracetamol&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> and D-Gal<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> in different animal models&#46;</p><p id="p0090" class="elsevierStylePara elsevierViewall">The current study showed that D-Gal caused a significant decrease in serum albumin level as an indicator of hepatotoxicity&#44; supporting the previous study of Wong&#44; <span class="elsevierStyleItalic">et al</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Moreover&#44; it is has been shown that the lowering of serum albumin level is attributed to the reduction of albumin mRNA expression&#44; this report observed that there was an abrupt decrease of albumin mRNA which was maximum at the day two after D-Gal administration&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Noteworthy&#44; the present data showed that pretreatment with PTX significantly inhibited the reduction in serum albumin in D-Gal treated rats compared to control rats&#46; This effect could be explained by ability of PTX to increase the blood flow and irrigation to liver and this might contribute in returning liver vitality&#46; The same effect of PTX on serum albumin level was previously reported&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="p0095" class="elsevierStylePara elsevierViewall">On the other hand&#44; D-Gal caused an increase in serum ALP compared to non-treated control group&#46; This rise in serum ALP activity may be attributed to the disturbance in the secretory activity or in the transport of metabolites or may be due to altered synthesis of certain enzymes as in other hepatotoxic conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> The present finding is in accordance with the result of a previous report of Abdel Salam&#44; <span class="elsevierStyleItalic">et al</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> demonstrating an increase of ALP activity in carbon tetrachloride and acetaminophen models of liver injury Serum ALP activity in PTX pretreated group was returned to approximately its normal level compared to D-Gal treated group&#46; This effect&#44; also&#44; was comparable to the effect of SYM on ALP activity in serum&#44; in accordance to the study reported by Peterson&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> We suggest that the bile duct-obstruction may cause more pronounced elevation in ALP activity as ALP is mainly produced in bile duct and its release is enhanced by cholestasis&#46; Thus&#44; PTX failed in preventing that effect&#46;</p><p id="p0100" class="elsevierStylePara elsevierViewall">In the current work&#44; administration of single dose of D-Gal caused non significant decrease in triglycerides concentration in the liver&#44; this effect may be due to impairment of hepatic synthesis of triglycerides&#46; Kattermann and Sirowej demonstrated that such decrease could be attributed to sex differences in the fatty liver induced by D-Gal&#44; and the level of hepatic triglycerides content decreased especially in male animals rather than females&#46;</p><p id="p0105" class="elsevierStylePara elsevierViewall">Oxidative stress and lipid peroxidation that are mediated by oxygen free radicals has been implicated as a common link between chronic liver damage and hepatic fibrosis&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Hepatocytes are well recognized as being continuously exposed to reactive oxygen species in various liver diseases including cholestasis&#46; Antioxidant molecules such as glutathione &#40;GSH&#41; and antioxidative enzymes such SOD&#44; and CAT ordinarily provide hepatocytes with resistance to oxidative stresses&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> The reduction of oxidative stress by PTX might be important because increased oxidative stress is a feature of the CCl4-induced liver injury and significant protection was obtained with the use of antioxidants&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="p0110" class="elsevierStylePara elsevierViewall">Notably&#44; our study revealed that the single intraperitoneal administration of D-Gal resulted in a significant reduction of tissue catalase and superoxide dismutase activity in addition to elevated level of thiobarbituric acid reactive species &#40;TBARs&#41; as a biochemical marker of lipid peroxidation&#46; It has been suggested that oxygen derived free radicals released from activated hepatic macrophages are the primary cause of D-Gal induced liver damage&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> However&#44; Wong&#44; <span class="elsevierStyleItalic">et al</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> reported an increase in SOD activity which contradicts the present results&#46; They speculated that the upregulation of SOD activity may be attributed to adaptive mechanisms to counteract increased oxidative stress&#46;</p><p id="p0115" class="elsevierStylePara elsevierViewall">There are several studies reporting the relevance of CAT to hepatic fibrosis i&#46;e&#46; CAT blocked Tumor Growth Factor B1 &#40;TGF-B1&#41; and collagen production in hepatic stellate cells&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> CAT activity was reduced in human hepatic injury and cirrhosis<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> and overexpression of CAT rescued hepatic damage<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a>&#46; A possible explanation of the effect of D-Gal on CAT activity is the assumption that the impairment of CAT activity might be the cause rather than a consequence of D-Gal hepatotoxicity&#46; Thus&#44; the increase in oxidative stress caused by impaired CAT activity is likely a key element of triggering hepatic fibrosis&#46; This is in agreement with the reported effect of thioacetamide &#40;another hepatotoxic agent&#41; on catalase activity&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> The reduction of CAT activity observed in D-Gal treated group in the study was&#44; also&#44; reported in pervious studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">35</span></a>-<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> Pretreatment with PTX prevented D-Gal induced reduction of antioxidative enzymes&#44; SOD and CAT and attenuated the elevated MDA level in hepatic tissue&#44; which observed in control group&#46; This effect may be due to increased blood flow to liver which increases its antioxidant capacity in addition of direct antioxidant effect of PTX and its metabolites&#46; As SYM has strong antioxidative properties and is able to scavenge both free radicals and reactive oxygen species&#44; so it exhibited the same results observed with PTX pretreated group&#46;</p><p id="p0120" class="elsevierStylePara elsevierViewall">There is good evidence that cyclic nucleotides are able to prevent oxidative stress by reduction of lipid peroxidation&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> Demir and Inal-Erden<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> explained the effects of PTX on production of free radicals to be linked with leukocyte-driven radicals&#46; PTX can enhance the chemotactic response of neutrophils&#46; PTX&#44; also&#44; may inhibit the phagocytosis and superoxide production by neutrophils and monocytes&#46; Savas&#44; <span class="elsevierStyleItalic">et al</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> reported that PTX reduced levels of MDA as well as SOD and CAT activities in a rabbit model of ischemia-reperfusion injury&#44; they attributed these effects to their assumption that PTX is a free radical scavenger and neutrophils stabilizer&#46; Thus&#44; PTX decreases free radical production&#44; antioxidant enzymes and cytokines released from the activated neutrophils&#46; Collectively&#44; these reports support the hypothsis that PTX might exert its hepatotprotective effects due its antioxidant properties&#46;</p><p id="p0125" class="elsevierStylePara elsevierViewall">Nitric oxide plays a role in pro-inflammatory cell signaling&#44; altering cellular gene expression&#44; enzyme activity and transcription factor activity&#46; In addition&#44; NO regulates vasodilatation&#44; platelets and neutrophils aggregation&#44; and local organ blood flow&#46; Therefore&#44; NO influences cell and tissue function&#46; The present study revealed that D-Gal induced hepatic injury was associated with elevated NO level&#46; On the other hand&#44; it has been shown that administration of NO donors provides cytoprotection from inflammatory liver damage and hepatocellular apoptosis&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> However&#44; pharmacological blockade of iNOS either aggravates or attenuates liver injury or is ineffective&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> Interestingly&#44; the present results showed that PTX as well as SYM reduced the total level of nitrate&#47;nitrite &#40;the stable metabolite of NO&#41;&#46; Such reduction was significant compared to results of non pretreated D-Gal group&#46;</p><p id="p0130" class="elsevierStylePara elsevierViewall">Histological changes&#44; especially acute inflammatory response was visible throughout many lobules&#46; The present data suggest that PTX produced protective effects against the disturbed biochemical markers and histopathological findings of D-Gal induced hepatotoxicity in rat model&#46; PTX reduced the levels of toxic free radical and attenuated NO production Thus&#44; PTX increases hepatic antioxidant enzyme activities&#44; and its antioxidant effect appears to play a key role in the attenuation of inflammation&#46; The present results may indicate that PTX and SYM have an antioxidant effect on the increase of the SOD and CAT activities&#46; The combination of PTX with SYM might not provide additional benefits when compared to the use of PTX or SYM alone in the maintenance of antioxidant defense of liver tissues&#46;</p><p id="p0135" class="elsevierStylePara elsevierViewall">In conclusion&#44; these results indicate that PTX attenuated the hepatic damage-induced by D-Gal by reducing oxidative stress and increasing the antioxidant defense activities&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Acknowledgment</span><p id="p0140" class="elsevierStylePara elsevierViewall">We thanks Prof&#46; Mohamed Hamid&#44; Vet Medicine&#44; Zagaig University&#44; for his kind help in histopathology study&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:8 [
        0 => array:3 [
          "identificador" => "xres1217517"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abs0010"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1132898"
          "titulo" => "Key words"
        ]
        2 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        3 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Material and Methods"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Animals"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Experimental procedures"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Histopathological examination"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        4 => array:3 [
          "identificador" => "sec0035"
          "titulo" => "Results"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Effects of PTX on the serum albumin and ALP levels"
            ]
            1 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Effect of PTX on the hepatic oxidative stress markers"
            ]
            2 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Effect of PTX on the hepatic lipid peroxidation and total nitrite levels"
            ]
            3 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Histopathological examination"
            ]
          ]
        ]
        5 => array:2 [
          "identificador" => "sec0060"
          "titulo" => "Discussion"
        ]
        6 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Acknowledgment"
        ]
        7 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2009-10-22"
    "fechaAceptado" => "2009-11-13"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Key words"
          "identificador" => "xpalclavsec1132898"
          "palabras" => array:4 [
            0 => "D-galactosamine"
            1 => "Hepatotoxicty"
            2 => "Pentoxifylline"
            3 => "Antioxidant"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">The present study was conducted to investigate effect of pentoxifylline &#40;PTX&#41; on acute liver injury caused by galactosamine &#40;D-Gal&#41; in rats and the underlying mechanism involved in this setting&#46; Moreover&#44; we attempted to compare its effect to the well-established hepatoprotective agent&#44; silymarin &#40;SYM&#41;&#46; The rats were randomly assigned 5 groups&#44; control&#44; PTX-treated &#40;100 mg&#47;kg&#44; 3 weeks&#41;&#44; SYM-treated &#40;100 mg&#47;kg&#44; 3 weeks&#41; and their combination&#46; Hepatic injury was induced by intraperitoneal single dose injection of D-Gal &#40;800 mg&#47;kg&#41;&#46; Hepatic functions parameters&#44; including serum albumin and alkaline phosphatase &#40;ALP&#41; levels were determined&#46; Antioxidants enzyme activities such as superoxide dismutase &#40;SOD&#41;&#44; catalase &#40;CAT&#41; as well as lipid peroxides and hepatic total nitrites were measured&#46; Besides&#44; histopathological examination was also performed using portions of liver tissues&#46; Results showed that the liver injury induced by D-Gal was improved in the three pretreated groups to variable extents&#46; Pretreatment with PTX prevented D-Gal-induced reduction of antioxidante enzyme activities&#44; SOD and CAT&#44; and attenuated the elevated malonaldahyde &#40;MDA&#41; level in hepatic tissue as marker of lipid peroxidation&#46; In addition&#44; pretreatment with PTX resulted in an increase in hepatic triglycerides&#44; normalization of nitric oxide level&#44; and lowering serum ALP activity as well as inhibited the decreased serum albumin level caused by D-Gal&#46; These biochemical changes were reflected on attenuation the structural alterations of the liver integrity&#46; Collectively&#44; our data suggest that PTX exhibits a potential hepatoprotective effect against D-Gal-induced hepatotoxicity and this effect might be attributed to its antioxidant properties&#46;</p></span>"
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "f0005"
        "etiqueta" => "<span class="elsevierStyleBold"><span class="elsevierStyleItalic">Figure 1</span></span>"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 740
            "Ancho" => 2078
            "Tamanyo" => 249191
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Effect of D-Gal on the serum albumin and alkaline phosphatase levels in normal rats and rats pretreated with PTX&#44; SYM and their combination&#46; <span class="elsevierStyleBold">A&#46;</span> Effect of D-Gal on the serum albumin level in normal rats and rats pretreated with PTX&#44; SYM and their combination&#46; <span class="elsevierStyleBold">B&#46;</span> Effect of D-Gal on the serum alkaline phosphatase in normal rats pretreated with either PTX or SYM or their concurrent administration&#46; Values of each bar represent the mean &#177; SEM of 7 observations&#46; <span class="elsevierStyleBold">&#42;</span>Statistically significant of D-Gal-treated group from control group at the significance level p &#60; 0&#46;05&#46; &#35;&#44; f&#44; &#948; Statistically significant of PTX&#44; SYM and &#40;PTX and SYM&#41; versus D-Gal-treated group&#44; respectively&#44; at the significance level p &#60; 0&#46;05&#46; <span class="elsevierStyleBold">D-Gal&#58;</span> D-Galactosamine&#46; <span class="elsevierStyleBold">PTX&#58;</span> Pentoxifylline&#46; <span class="elsevierStyleBold">SYM&#58;</span> Silymarin&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "f0010"
        "etiqueta" => "<span class="elsevierStyleBold"><span class="elsevierStyleItalic">Figure 2</span></span>"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 740
            "Ancho" => 2077
            "Tamanyo" => 247854
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Effect of D-Gal on antioxidant enzyme activates of liver tissue in normal rats and those pretreated with PTX&#44; SYM and their combination&#46; <span class="elsevierStyleBold">A&#46;</span> Effect of D-Gal on CAT of liver tissue in normal rats and those pretreated with either PTX or SYM or their combination&#46; <span class="elsevierStyleBold">B&#46;</span> Effect of D-Gal on CAT of liver tissue in normal rats pretreated with PTX&#44; SYM individually or in combined administration&#46; Values of each bar represent the mean &#177; SEM of 6 observations&#46; <span class="elsevierStyleBold">&#42;</span> Statistically significant of D-Gal-treated group from the control group at the significance level p &#60; 0&#46;05&#46; &#35;&#44; f&#44; &#948; Statistically significant of PTX&#44; SYM and &#40;PTX and SYM&#41; versus D-Gal-treated group&#44; respectively&#44; at the significance level p &#60; 0&#46;05&#46; <span class="elsevierStyleBold">CAT&#58;</span> Catalase&#46; <span class="elsevierStyleBold">SOD&#58;</span> Superoxide dismutase and other symbols as in <a class="elsevierStyleCrossRef" href="#f0005"><span class="elsevierStyleItalic">Figure 1</span></a>&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "f0015"
        "etiqueta" => "<span class="elsevierStyleBold"><span class="elsevierStyleItalic">Figure 3</span></span>"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 744
            "Ancho" => 2077
            "Tamanyo" => 226078
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Effect of D-Gal on hepatic lipid peroxidation and total nitrites in normal rats and those pretreated with PTX&#44; SYM and their combination&#46; <span class="elsevierStyleBold">A&#46;</span> Effect of D-Gal on the hepatic lipid peroxidation in normal rats pretreated with either PTX or SYM or their combination&#46; <span class="elsevierStyleBold">B&#46;</span> Effect of D-Gal on the hepatic total nitrites in normal rats pretreated with PTX and SYM individually or in concurrent administration&#46; Values of each bar represent the mean &#177; SEM of 7 observations&#46; <span class="elsevierStyleBold">&#42;</span> Statistically significant from the control group at the significance level p &#60; 0&#46;05&#46; &#35;&#44; f&#44; &#948; Statistically significant of PTX&#44; SYM and &#40;PTX and SYM&#41; versus D-Gal-treated group&#44; respectively&#44; at the significance level p &#60; 0&#46;05&#46; <span class="elsevierStyleBold">MDA&#58;</span> Malondialdhyde and other symbols as in <a class="elsevierStyleCrossRef" href="#f0005"><span class="elsevierStyleItalic">Figure 1</span></a>&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "f0020"
        "etiqueta" => "<span class="elsevierStyleBold"><span class="elsevierStyleItalic">Figure 4</span></span>"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 967
            "Ancho" => 1507
            "Tamanyo" => 357318
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Histopathological analysis to the effects D-Gal on liver in the absence or present of either PTX or SYM&#46; <span class="elsevierStyleBold">&#40;A&#41;</span> Liver of the control group illustrates normal parenchymal and sinusoidal structures&#44; H&#38;E&#46; <span class="elsevierStyleBold">&#40;B&#41;</span> Liver of D-Gal-treated group showing portal area with thickening and hyalinization of the tunica media of hepatic arteriole &#40;arrow&#41;&#44; H&#38;E&#46; x 500&#46; <span class="elsevierStyleBold">&#40;C&#41;</span> Liver PTX-treated group reveals portal area with congested blood vessel &#40;arrow head&#41; and few round cell infiltrations &#40;arrow&#41;&#44; HE x 300&#46; <span class="elsevierStyleBold">&#40;D&#41;</span> liver of SYM-treated group shows portal area with few round cell infiltrations &#40;arrow head&#41;&#44; HE x 300&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:42 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Teas and other beverages suppress D-galactosamine-induced liver injury in rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Sugiyama K&#46;"
                            1 => "He P&#46;"
                            2 => "Wada S&#46;"
                            3 => "Saeki S&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Xutr"
                        "fecha" => "1999"
                        "volumen" => "129"
                        "numero" => "7"
                        "paginaInicial" => "1361"
                        "paginaFinal" => "1367"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protective effect of Lygodium flexuosum &#40;L&#46;&#41; Sw&#46; &#40;Lygodiaceae&#41; against D-galactosamine induced liver injury in rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Wills P&#46;J&#46;"
                            1 => "Asha VV&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jep.2006.04.028"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Ethnopharmacol"
                        "fecha" => "2006"
                        "volumen" => "108"
                        "numero" => "1"
                        "paginaInicial" => "116"
                        "paginaFinal" => "123"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16797898"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunohistochemical study of extracellular matrix in acute galactosamine hepatitis in rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Jonker A&#46;M&#46;"
                            1 => "Dijkhuis F&#46;W&#46;"
                            2 => "Boes A&#46;"
                            3 => "Hardonk M&#46;J&#46;"
                            4 => "Grond J&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "1992"
                        "volumen" => "15"
                        "numero" => "3"
                        "paginaInicial" => "423"
                        "paginaFinal" => "431"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1371983"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Selective uridine triphosphate deficiency induced by D-galactosamine in liver and reversed by pyrimidine nucleotide precursors&#46; Effect on ribonucleic acid synthesis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Keppler D&#46;O&#46;"
                            1 => "Pausch J&#46;"
                            2 => "Decker K&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "1974"
                        "volumen" => "249"
                        "numero" => "1"
                        "paginaInicial" => "211"
                        "paginaFinal" => "216"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4809627"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protection by phosphodiesterase inhibitors against endotoxin-induced liver injury in galactosamine-sensitized mice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Fischer W&#46;"
                            1 => "Schudt C&#46;"
                            2 => "Wendel A&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/0006-2952(93)90219-m"
                      "Revista" => array:7 [
                        "tituloSerie" => "Biochem Pharmacol"
                        "fecha" => "1993"
                        "volumen" => "45"
                        "numero" => "12"
                        "paginaInicial" => "2399"
                        "paginaFinal" => "2404"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8392340"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protection by a cyclic AMP-specific phosphodiesterase inhibitor&#44; rolipram&#44; and dibutyryl cyclic AMP against Propionibacterium acnes and lipopolysaccharide-induced mouse hepatitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "Taguchi I&#46;"
                            1 => "Oka K&#46;"
                            2 => "Kitamura K&#46;"
                            3 => "Sugiura M&#46;"
                            4 => "Oku A&#46;"
                            5 => "Matsumoto M&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s000110050475"
                      "Revista" => array:7 [
                        "tituloSerie" => "Inflamm Res"
                        "fecha" => "1999"
                        "volumen" => "48"
                        "numero" => "7"
                        "paginaInicial" => "380"
                        "paginaFinal" => "385"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10450787"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effects of pentoxifylline on spinal cord blood flow after experimental spinal cord injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Thompson M&#46;K&#46;"
                            1 => "Tuma R&#46;F&#46;"
                            2 => "Young WF&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Assoc Acad Minor Phys"
                        "fecha" => "1999"
                        "volumen" => "10"
                        "numero" => "1"
                        "paginaInicial" => "23"
                        "paginaFinal" => "26"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10826005"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "In vivo effect of free radical scavenger hepatoprotective agents on superoxide dismutase &#40;SOD&#41; activity in patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Feher J&#46;"
                            1 => "Lang I&#46;"
                            2 => "Nekam K&#46;"
                            3 => "Gergely P&#46;"
                            4 => "Muzes G&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Tokai J Exp Clin Med"
                        "fecha" => "1990"
                        "volumen" => "15"
                        "numero" => "2-3"
                        "paginaInicial" => "129"
                        "paginaFinal" => "134"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2130521"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Silybin inhibition of amatoxin uptake in the perfused rat liver"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Faulstich H&#46;"
                            1 => "Jahn W&#46;"
                            2 => "Wieland T&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Arzneimittelforschung"
                        "fecha" => "1980"
                        "volumen" => "30"
                        "numero" => "3"
                        "paginaInicial" => "452"
                        "paginaFinal" => "454"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7387753"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The anti-inflammatory effects of the phosphodiesterase inhibitor pentoxifylline in the rat"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Abdel-Salam O&#46;M&#46;"
                            1 => "Baiuomy A&#46;R&#46;"
                            2 => "El-Shenawy S&#46;M&#46;"
                            3 => "Arbid MS&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Pharmacol Res"
                        "fecha" => "2003"
                        "volumen" => "47"
                        "numero" => "4"
                        "paginaInicial" => "331"
                        "paginaFinal" => "340"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12644391"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Microsomal lipid peroxidation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Buege J&#46;A&#46;"
                            1 => "Aust SD&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Methods Enzymol"
                        "fecha" => "1978"
                        "volumen" => "52"
                        "paginaInicial" => "302"
                        "paginaFinal" => "310"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/672633"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lipid peroxide and reactive oxygen species generating systems of the crystalline lens"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Babizhayev M&#46;A&#46;"
                            1 => "Costa EB&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/0925-4439(94)90014-0"
                      "Revista" => array:7 [
                        "tituloSerie" => "Biochimica et biophysica acta"
                        "fecha" => "1994"
                        "volumen" => "1225"
                        "numero" => "3"
                        "paginaInicial" => "326"
                        "paginaFinal" => "337"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8312381"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pectolinarin and Pectolinarigenin of Cirsium setidens Prevent the Hepatic Injury in Rats Caused by D-Galactosamine via an Antioxidant Mechanism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Yoo Y&#46;M&#46;"
                            1 => "Nam J&#46;H&#46;"
                            2 => "Kim M&#46;Y&#46;"
                            3 => "Choi J&#46;"
                            4 => "Park HJ&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Biol Pharm Bull"
                        "fecha" => "2008"
                        "volumen" => "31"
                        "numero" => "4"
                        "paginaInicial" => "760"
                        "paginaFinal" => "764"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18379079"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biochemical effects of the flavonolignane silibinin on RNA&#44; protein and DNA synthesis in rat livers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Sonnenbichler J&#46;"
                            1 => "Zetl I&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Prog Clin Biol Res"
                        "fecha" => "1986"
                        "volumen" => "213"
                        "paginaInicial" => "319"
                        "paginaFinal" => "331"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2424029"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protective and therapeutic effect of silymarin on the development of latent liver damage"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Kropacova K&#46;"
                            1 => "Misurova E&#46;"
                            2 => "Hakova H&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Radiats Biol Radioecol"
                        "fecha" => "1998"
                        "volumen" => "38"
                        "numero" => "3"
                        "paginaInicial" => "411"
                        "paginaFinal" => "415"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9682736"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevention by silymarin of membrane alterations in acute CCl4 liver damage"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Muriel P&#46;"
                            1 => "Mourelle M&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Appl Toxicol"
                        "fecha" => "1990"
                        "volumen" => "10"
                        "numero" => "4"
                        "paginaInicial" => "275"
                        "paginaFinal" => "279"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1975258"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Silymarin mediated differential modulation of toxicity induced by carbon tetrachloride&#44; paracetamol and D-galactosamine in freshly isolated rat hepatocytes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Chrungoo V&#46;J&#46;"
                            1 => "Singh K&#46;"
                            2 => "Singh J&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Indian J Exp Biol"
                        "fecha" => "1997"
                        "volumen" => "35"
                        "numero" => "6"
                        "paginaInicial" => "611"
                        "paginaFinal" => "617"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9357165"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protective activity of silipide on liver damage in rodents"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "Conti M&#46;"
                            1 => "Malandrino S&#46;"
                            2 => "Magistretti MJ&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Jpn J Pharmacol"
                        "fecha" => "1992"
                        "volumen" => "60"
                        "numero" => "4"
                        "paginaInicial" => "315"
                        "paginaFinal" => "320"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1287266"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The cytoprotective effect of alpha-tocopherol and daidzein against d-galactosamine-induced oxidative damage in the rat liver"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:5 [
                            0 => "Wong M&#46;C&#46;"
                            1 => "Portmann B&#46;"
                            2 => "Sherwood R&#46;"
                            3 => "Niemela O&#46;"
                            4 => "Koivisto H&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.metabol.2007.01.005"
                      "Revista" => array:8 [
                        "tituloSerie" => "Metabolism"
                        "fecha" => "2007"
                        "volumen" => "56"
                        "numero" => "7"
                        "paginaInicial" => "865"
                        "paginaFinal" => "875"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17570244"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673615010375"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Activation&#44; proliferation&#44; and differentiation of progenitor cells into hepatocytes in the D-galactosamine model of liver regeneration"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Dabeva M&#46;D&#46;"
                            1 => "Shafritz DA&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Pathol"
                        "fecha" => "1993"
                        "volumen" => "143"
                        "numero" => "6"
                        "paginaInicial" => "1606"
                        "paginaFinal" => "1620"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7504886"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pentoxifylline prevents fibrosis in an animal model and inhibits platelet-derived growth factor-driven proliferation of fibroblasts"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Peterson TC&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "1993"
                        "volumen" => "17"
                        "numero" => "3"
                        "paginaInicial" => "486"
                        "paginaFinal" => "493"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8095247"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nature of inhibition of rat testicular alkaline phosphatase by isatin"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Kumar P&#46;"
                            1 => "Nagpaul J&#46;P&#46;"
                            2 => "Singh B&#46;"
                            3 => "Bansal R&#46;C&#46;"
                            4 => "Sharma R&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/bf01935909"
                      "Revista" => array:7 [
                        "tituloSerie" => "Experientia"
                        "fecha" => "1978"
                        "volumen" => "34"
                        "numero" => "4"
                        "paginaInicial" => "434"
                        "paginaFinal" => "435"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/639934"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of pentoxifylline on hepatic injury caused in the rat by the administration of carbon tetrachloride or acetaminophen&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Abdel S&#46;O&#46;M&#46;"
                            1 => "Baiuomy A&#46;R&#46;"
                            2 => "El-Shenawy S&#46;M&#46;"
                            3 => "Hassan NS&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Pharmacol Rep"
                        "fecha" => "Sep-Oct 2005"
                        "volumen" => "57"
                        "numero" => "5"
                        "paginaInicial" => "596"
                        "paginaFinal" => "603"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16227642"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Liver injury and lipid metabolism&#58; sex differences in the fatty liver induced by d-galactosamine"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Kattermann R&#46;"
                            1 => "Sirowej H&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Hepatogastroenterol &#40;Stuttg&#41;"
                        "fecha" => "1979"
                        "volumen" => "2"
                        "numero" => "26"
                        "paginaInicial" => "112"
                        "paginaFinal" => "126"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatoprotective and antifibrotic effect of a new silybin-phosphatidylcholine-Vitamin E complex in rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Di Sario A&#46;"
                            1 => "Bendia E&#46;"
                            2 => "Taffetani S&#46;"
                            3 => "Omenetti A&#46;"
                            4 => "Candelaresi C&#46;"
                            5 => "Marzioni M&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.dld.2005.05.011"
                      "Revista" => array:7 [
                        "tituloSerie" => "Dig Liver Dis"
                        "fecha" => "2005"
                        "volumen" => "37"
                        "numero" => "11"
                        "paginaInicial" => "869"
                        "paginaFinal" => "876"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16169303"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Role of ursodeoxycholic acid in prevention of hepatotoxicity caused by amoxicillin-clavulanic acid in rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "El-Sherbiny G&#46;A&#46;"
                            1 => "Taye A&#46;"
                            2 => "Abdel-Raheem IT&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Ann Hepatol"
                        "fecha" => "2009"
                        "volumen" => "8"
                        "numero" => "2"
                        "paginaInicial" => "134"
                        "paginaFinal" => "140"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19502657"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Responses of antioxidant systems in the hepatocytes of common carp &#40;Cyprinus carpio L&#46;&#41; to the toxicity of microcystin-LR"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Li X&#46;"
                            1 => "Liu Y&#46;"
                            2 => "Song L&#46;"
                            3 => "Liu J&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Toxicon"
                        "fecha" => "2003"
                        "volumen" => "42"
                        "numero" => "1"
                        "paginaInicial" => "85"
                        "paginaFinal" => "89"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12893065"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo&#58; the protective effect of allopurinol"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Jaeschke H&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Pharmacol Exp Ther"
                        "fecha" => "1990"
                        "volumen" => "255"
                        "numero" => "3"
                        "paginaInicial" => "935"
                        "paginaFinal" => "941"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2262912"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Modulation of hepatotoxicity by macrophages in the liver"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Shiratori Y&#46;"
                            1 => "Kawase T&#46;"
                            2 => "Shiina S&#46;"
                            3 => "Okano K&#46;"
                            4 => "Sugimoto T&#46;"
                            5 => "Teraoka H&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Hepatology"
                        "fecha" => "1988"
                        "volumen" => "8"
                        "numero" => "4"
                        "paginaInicial" => "815"
                        "paginaFinal" => "821"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2839405"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Changes in free radicals&#44; trace elements&#44; and neurophysiological function in rats with liver damage induced by D-galactosamine"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Hu H&#46;L&#46;"
                            1 => "Chen RD&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/BF02783894"
                      "Revista" => array:7 [
                        "tituloSerie" => "Biol Trace Elem Res"
                        "fecha" => "1992"
                        "volumen" => "34"
                        "numero" => "1"
                        "paginaInicial" => "19"
                        "paginaFinal" => "25"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1382518"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glutathione levels discriminate between oxidative stress and transforming growth factor-beta signaling in activated rat hepatic stellate cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "De Bleser P&#46;J&#46;"
                            1 => "Xu G&#46;"
                            2 => "Rombouts K&#46;"
                            3 => "Rogiers V&#46;"
                            4 => "Geerts A&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.274.48.33881"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "1999"
                        "volumen" => "274"
                        "numero" => "48"
                        "paginaInicial" => "33881"
                        "paginaFinal" => "33887"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10567349"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antioxidant enzyme status in biliary obstructed rats&#58; effects of N-acetylcysteine"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Pastor A&#46;"
                            1 => "Collado P&#46;S&#46;"
                            2 => "Almar M&#46;"
                            3 => "Gonzalez-Gallego J&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "J Hepatol"
                        "fecha" => "1997"
                        "volumen" => "27"
                        "numero" => "2"
                        "paginaInicial" => "363"
                        "paginaFinal" => "370"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9288612"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Adenovirus-mediated overexpression of catalase in the cytosolic or mitochondrial compartment protects against cytochrome P450 2E1-dependent toxicity in HepG2 cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Bai J&#46;"
                            1 => "Cederbaum Al&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.M008895200"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2001"
                        "volumen" => "276"
                        "numero" => "6"
                        "paginaInicial" => "4315"
                        "paginaFinal" => "4321"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11071897"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "PPARalpha ligands activate antioxidant enzymes and suppress hepatic fibrosis in rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Toyama T&#46;"
                            1 => "Nakamura H&#46;"
                            2 => "Harano Y&#46;"
                            3 => "Yamauchi N&#46;"
                            4 => "Morita A&#46;"
                            5 => "Kirishima T&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bbrc.2004.09.110"
                      "Revista" => array:8 [
                        "tituloSerie" => "Biochem Biophys Res Commun"
                        "fecha" => "2004"
                        "volumen" => "324"
                        "numero" => "2"
                        "paginaInicial" => "697"
                        "paginaFinal" => "704"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15474484"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S1470204512703790"
                          "estado" => "S300"
                          "issn" => "14702045"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatoprotective effect of Picrorrhiza kurroa on tissue defence system in-galactosamine-induced hepatitis in rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Anandan R&#46;"
                            1 => "Devaki T&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Fitoterapia"
                        "fecha" => "1999"
                        "volumen" => "70"
                        "numero" => "1"
                        "paginaInicial" => "54"
                        "paginaFinal" => "57"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antihepatotoxic potential of Sargassum polycystum &#40;Phaeophyceae&#41; on antioxidant defense status in Dgalactosamine-induced hepatitis in rats"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "Meena B&#46;"
                            1 => "Anbin E&#46;R&#46;"
                            2 => "Rajesh R&#46;"
                            3 => "Sheik H&#46;A&#46;"
                            4 => "Ganesan B&#46;"
                            5 => "Anandan R&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Afr J Biochem Res"
                        "fecha" => "2008"
                        "volumen" => "2"
                        "numero" => "2"
                        "paginaInicial" => "51"
                        "paginaFinal" => "55"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hepatoprotective effect of allicin on tissue defense system in galactosamine&#47;endotoxin challenged rats&#46;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Vimal V&#46;"
                            1 => "Devaki T&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:8 [
                        "tituloSerie" => "J Ethnopharmacol"
                        "fecha" => "2004"
                        "volumen" => "90"
                        "numero" => "1"
                        "paginaInicial" => "151"
                        "paginaFinal" => "154"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14698523"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0090429516305519"
                          "estado" => "S300"
                          "issn" => "00904295"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Protection by sildenafil and theophylline of lead acetate-induced oxidative stress in rat submandibular gland and saliva"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Abdollahi M&#46;"
                            1 => "Fooladian F&#46;"
                            2 => "Emami B&#46;"
                            3 => "Zafari K&#46;"
                            4 => "Bahreini-Moghadam A&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1191/0960327103ht399oa"
                      "Revista" => array:7 [
                        "tituloSerie" => "Hum Exp Toxicol"
                        "fecha" => "2003"
                        "volumen" => "22"
                        "numero" => "11"
                        "paginaInicial" => "587"
                        "paginaFinal" => "592"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14686481"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pentoxifylline and N-acetylcysteine in hepatic ischemia&#47;reperfusion injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Demir S&#46;"
                            1 => "lnal-Erden M&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Chim Acta"
                        "fecha" => "1998"
                        "volumen" => "275"
                        "numero" => "2"
                        "paginaInicial" => "127"
                        "paginaFinal" => "135"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9721071"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pentoxifylline reduces biochemical markers of ischemia-reperfusion induced spinal cord injury in rabbits"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Savas S&#46;"
                            1 => "Delibas N&#46;"
                            2 => "Savas C&#46;"
                            3 => "Sutcu R&#46;"
                            4 => "Cindas A&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/sj.sc.3101281"
                      "Revista" => array:7 [
                        "tituloSerie" => "Spinal Cord"
                        "fecha" => "2002"
                        "volumen" => "40"
                        "numero" => "5"
                        "paginaInicial" => "224"
                        "paginaFinal" => "229"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11987004"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inducible nitric oxide synthase is critical for immune-mediated liver injury in mice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Sass G&#46;"
                            1 => "Koerber K&#46;"
                            2 => "Bang R&#46;"
                            3 => "Guehring H&#46;"
                            4 => "Tiegs G&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI10613"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2001"
                        "volumen" => "107"
                        "numero" => "4"
                        "paginaInicial" => "439"
                        "paginaFinal" => "447"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11181643"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Nitric Oxide&#46; IV&#46; Determinants of nitric oxide protection and toxicity in liver"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Li J&#46;"
                            1 => "Billiar TR&#46;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/ajpgi.1999.276.5.G1069"
                      "Revista" => array:7 [
                        "tituloSerie" => "Am J Physiol"
                        "fecha" => "1999"
                        "volumen" => "276"
                        "numero" => "5 Pt 1"
                        "paginaInicial" => "G1069"
                        "paginaFinal" => "G1073"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10329995"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/16652681/0000000800000004/v1_201907070733/S166526811931751X/v1_201907070733/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "77721"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original Article"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/16652681/0000000800000004/v1_201907070733/S166526811931751X/v1_201907070733/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S166526811931751X?idApp=UINPBA00004N"
]

Article information

ISSN: 16652681
Original language: English

DOI:10.1016/S1665-2681(19)31751-X

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	3	1	4
2024 October	18	5	23
2024 September	17	5	22
2024 August	17	8	25
2024 July	13	4	17
2024 June	6	4	10
2024 May	15	7	22
2024 April	14	3	17
2024 March	30	5	35
2024 February	48	6	54
2024 January	15	6	21
2023 December	21	9	30
2023 November	24	8	32
2023 October	39	11	50
2023 September	20	4	24
2023 August	17	4	21
2023 July	11	3	14
2023 June	23	3	26
2023 May	39	9	48
2023 April	54	2	56
2023 March	73	4	77
2023 February	21	5	26
2023 January	7	4	11
2022 December	20	3	23
2022 November	22	4	26
2022 October	15	5	20
2022 September	24	7	31
2022 August	15	7	22
2022 July	21	7	28
2022 June	12	7	19
2022 May	11	9	20
2022 April	14	13	27
2022 March	23	18	41
2022 February	38	7	45
2022 January	42	12	54
2021 December	24	25	49
2021 November	20	23	43
2021 October	23	16	39
2021 September	7	7	14
2021 August	10	10	20
2021 July	14	11	25
2021 June	14	11	25
2021 May	10	9	19
2021 April	22	11	33
2021 March	6	5	11
2021 February	6	5	11
2021 January	12	11	23
2020 December	9	4	13
2020 November	15	2	17
2020 October	9	4	13
2020 September	5	10	15
2020 August	10	1	11
2020 July	4	0	4
2020 June	7	2	9
2020 May	7	3	10
2020 April	1	2	3
2020 March	8	5	13
2020 February	8	0	8
2020 January	3	4	7
2019 December	10	7	17
2019 November	5	0	5
2019 October	2	5	7
2019 September	1	1	2
2019 August	1	1	2
2019 July	1	3	4

Show all

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter