Background and aim: Ischemia-reperfusion (IR) injury is one of the leading causes of early graft dysfunction in liver transplantation. Techniques such as ischemic preconditioning protect the graft through the activation of the hypoxia-inducible factors, which are the main regulators of oxygen homeostasis and are downregulated by the EGLN prolyl-hydroxylases. The inhibition of EGLN has a therapeutic effect against IR injury. Our aim was to evaluate the effect of the EGLN inhibitor sodium (S)-2-hydroxyglutarate [(S)-2HG] against liver IR injury in Wistar rats.
Material and methods: (S)-2HG was synthesized from L-glutamic acid by diazotization/alkaline hydrolysis, and its structure was confirmed by nuclear magnetic resonance. Thirty-one female Wistar rats were used, weighing 250 – 300g, randomly divided in the following groups, following the specifications of the NOM-062-ZOO-1999: IR (n=7, ischemia: 20minutes, reperfusion: 60minutes), sham (SH, n=7, laparotomy without IR), non-toxicity (HGTox, n=6, 25mg/kg, p.o., twice per day for two days, laparotomy without IR), and (S)-2HG+IR (HGIR, n=7, same dose as HGTox group+IR induction). Serum levels of ALT, AST, LDH, ALP, glucose, and total bilirubin, were assessed. Tissue levels of IL-1β, IL-6, TNF-α, malondialdehyde, SOD, and glutathione peroxidase were also evaluated. This project was approved by the Ethics and Research Committee of our institution (Registration number: HI19-00003).
Results: A difference in the levels of ALT, AST, LDH, glucose, IL-1β, and IL-6 was observed among the groups (Figure). No hepatotoxic effect was observed when comparing the HGTox group versus the SH group. There were also no differences in the other biomarkers assessed.
Liver injury and inflammatory biomarkers. (A) Serum alanine aminotransferase; (B) Serum aspartate aminotransferase; (C) Serum lactate dehydrogenase; (D) Serum glucose; (E) Tissue interleukin 1β; (F) Tissue interleukin 6. One-way ANOVA with Tukey post hoc test, *p<0.05 versus SH; #p<0.05 versus IR.
Conclusions: (S)-2HG showed a hepatoprotective effect, decreasing the levels of liver injury and inflammation biomarkers. No hepatotoxic effect was observed at the tested dose.
Conflicts of interest: The authors have no conflicts of interest to declare.
