Obestatin improves hepatic injury induced by ischemia/reperfusion in rats: Role of nitric oxide.

Hepatic ischemia/reperfusion (I/R) injury is a common clinical problem. The present study was conducted to evaluate the protective effect of obestatin against I/R-induced liver injury. Rats were divided into three groups (n = 10): control sham-operated group, I/R group and obestatin treatment group. Rats of I/R group and obestatin treatment group underwent partial hepatic ischemia for 60 min followed by 90 min reperfusion. At the beginning of the 90-min reperfusion period, rats of obestatin treatment group were injected with obestatin (100 μg/kg) intravenously. At the end of the experiment the animals were sacrificed and blood and liver tissue samples were obtained. Liver function enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as inflammatory biomarkers, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were determined in the serum. Also, total oxidative status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI) were measured in hepatic tissue. Liver tissue damage was examined by histopathology. In addition, the expression levels of nitric oxide synthase (NOS) subtypes, endothelial (eNOS) and inducible (iNOS) in liver samples were assessed by Western blotting. Obestatin significantly counteracted I/R-induced liver damage mainly through reducing oxidative stress, inhibiting the release of pro-inflammatory cytokines and modulation of nitric oxide levels.