Effect of Obestatin on Hepatic Injury Induced by Renal Ischemia/Reperfusion in Rat

Abstract

Background and Aims: Oxygen free radicals and cytokines are considered to be important components involved in the pathophysiological tissue alterations observed during Ischemia/Reperfusion (I/R). Based on the anti-oxidant and antiinflammatory effects of Obestatin (OB), we investigated the putative protective role of OB against I/R-induced oxidative remote organ injury. Materials and Methods: Male albino rats were subjected to either sham operation or bilateral renal artery clamping for 45 min and reperfusion for 24 h to induce I/R damage. Obestatin was administered intraperitoneally twice a day at a dose of 8 nmol/kg. At the end of the experimental procedure, the rats were decapitated and hepatic tissue were removed for biochemical analyses of: Malondialdehyde (MDA), an end product of lipid peroxidation; the activity of antioxidant enzymes Superoxide Dismutase (SOD) and Catalase (CAT); the Myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration and the level of pro-inflammatory cytokines (TNF-α and IL-1β). The serum Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Lactate Dehydrogenase (LDH) levels were measured to assess liver function and tissue damage, respectively. Pathological histology was also performed. Results: The results revealed the occurrence of I/R- induced oxidative organ damage, as confirmed histologically and evidenced by an increase in the MDA level and MPO activity, and a decrease in activity of SOD and CAT. Furthermore, serum AST, ALT, LDH levels, and tissue cytokines were elevated in the renal I/R group as compared to the sham operated control group. On the other hand, obestatin treatment succeeded to modulate these observed abnormalities resulting from I/R as indicated by the reduction of MAD and the pronounced improvement of the investigated biochemical and antioxidant parameters. Conclusion: Since obestatin administration reversed these oxidant responses, it seems likely that obestatin has a protective effect against oxidative organ damage induced by I/R.