The aim of this study was to investigate the comparative protective effects of separate and combined pretreatment with Cr and ZnSO4 on serum levels of miR-122, miR-34a, liver function tests, protein expression of Nrf2 and p53, and histopathological changes following IR-induced hepatic injury.

Fifty-six male Wistar rats randomly assigned into seven groups (n=8). Sham (S), IR, crocin pretreatment (Cr), and crocin pretreatment+IR (Cr+IR), ZnSO4 pretreatment (ZnSO4), ZnSO4 pretreatment+IR (ZnSO4+IR) and their combination (Cr+ZnSO4+IR) groups. In sham, ZnSO4 and Cr groups, animals received normal saline (N/S, 2ml/day), Cr (200mg/kg) and ZnSO4 (5mg/kg) for 7 consecutive days (intraperitoneally; i.p), then only laparotomy was performed. In IR, Cr+IR, ZnSO4+IR and Cr+ZnSO4+IR groups, rats received N/S, Cr and ZnSO4 with same dose and time, then underwent a partial (70%) ischemia for 45min that followed by reperfusion for 60min. Blood sample was taken for biochemical and microRNAs assay, tissue specimens were obtained for antioxidants, protein expression, histopathological and immunohistochemical evaluations.

The results showed that Cr and ZnSO4 increased antioxidants activity and expression of Nrf2, decreased serum levels of liver enzymes, miR-122, miR-34a, p53 expression and also ameliorated histopathological abnormality. However, their combination caused more improvement on IR-induced liver injury.

This study demonstrated that Cr, ZnSO4 and their combination through increasing antioxidant activity and Nrf2 expression, decreasing the serum levels of liver enzymes, miR-122, 34a, p53 expression, and amelioration of histopathological changes, protected liver against IR-induced injury.