The Effect of Zinc Sulfate on miR-122, miR-34a, Atioxidants, Biochemical and Histopathological Parameters Following Hepatic Ischemia/Reperfusion Injury in Rats

Liver ischemia-reperfusion (IR) injury is a situation which occurs in various conditions such as pringle maneuver and liver transplantation. The regulatory effect of zinc sulfate (ZnSO4) is an important trace element on several liver disorders well known, but its effects on microRNA(S) (miR-122 and miR-34a) have not been evaluated. The goal of this study was to identify the protective effects of ZnSO4 on IR-induced liver injury, in particular, microRNA(S) in rats. Thirty-two male Wistar rats were randomly assigned into four groups (eight each group): sham, IR, ZnSO4 pretreatment, and ZnSO4 + IR groups. In sham and ZnSO4 pretreatment groups, animals received normal saline (N/S, 2ml/kg) and ZnSO4 (5mg/kg) for 7 consecutive days intraperitoneally (ip), then only laparotomy was performed. In IR and ZnSO4 + IR groups, N/S and ZnSO4, respectively, were given with the same dose, time, and route, before induction of ischemia for 45min followed by reperfusion for 60min. Blood sample was taken for biochemical and microRNAs analysis. Tissue specimens also were obtained for the measurements of antioxidant activities and histopathological evaluations. Our results showed that ZnSO4 pretreatment ameliorated histopathological changes decreased the increased serum levels of liver enzymes, miR-122 and miR-34a, and enhanced the decreased activity of antioxidant enzymes following hepatic IR injury. The present study indicated that ZnSO4 had potential hepatoprotective action against IR-induced injury. Therefore, it has been suggested that it can be administered as an anti-miR before elective hepatic surgeries for prevention of this complication.