Background and aim: The relationship between the liver and the kidneys in some hepatic diseases is well known. Hepatorenal syndrome usually occurs in chronic damage but has also been observed in the acute one. Therapeutic approaches remain limited and poorly optimized, especially to address the commitment of both organs. HGF induces protection in various organs, but its effects are unknown in a scenario of multi-organ compromise, as in the case of hepatorenal syndrome or colemic nephropathy. The aim of this investigation was to determine the mechanism induced by HGF to counteract liver and kidney damage in a preclinical model of systemic damage induced by intrahepatic cholestasis in a setting of colemic nephropathy.
Material and methods: CD-1 mice were treated with α-naphthyl isothiocyanate (ANIT, 60μg / kg, i.g.) for 48h. After 24h of ANIT treatment, HGF (10μg / kg, i.v.) was administered. Mice were throughout treatment in metabolic cages. Urine samples were collected from the last 12h of treatment. After 48h, mice were sacrificed, blood and tissue were obtained. Liver function tests (ALP, GGT and bile salts), analysis of bile transporter expression by qRT-PCR, serum and urine creatinine content, albuminuria and HSP27 in urine, and H-E staining were performed, ROS content was addressed in kidney tissue.
Results: Cholestasis induced by ANIT was corroborated by the increase of bile salts in the liver and serum, and the increase in GGT and ALP. Interestingly, we found renal dysfunction determined by the increase in serum creatinine, and decrease in its clearance, as well as proteinuria and the increase in urine HSP72. Treatment with HGF reduced to control values the markers of liver and kidney damage, significantly improving renal histology. The protection mechanism was closely associated with the control of oxidative damage. In conclusion, HGF is presented as a therapeutic intervention point in cholestasis-mediated renal damage, counteracting the oxidative damage.
CONACYT: CB-A1-S-38154 y CB-252942.
Conflicts of interest: The authors have no conflicts of interest to declare.
