Hepatic ischemia reperfusion injury: effect of moderate intensity exercise and oxytocin compared to l-arginine in a rat model

Abstract

Background Hepatic ischemia reperfusion (IR) injury is considered as a main cause of liver damage and dysfunction. The l-arginine/nitric oxide pathway seems to be relevant during this process of IR. Although acute intense exercise challenges the liver with increased reactive oxygen species (ROS), regular training improves hepatic antioxidant status. Also, oxytocin (Oxy), besides its classical functions, it exhibits a potent antistress, anti-inflammatory, and antioxidant effects. This study was designed to evaluate the hepatic functional and structural changes induced by hepatic IR injury in rats and to probe the effect and potential mechanism of moderate intensity exercise training and/or Oxy, in comparison to a nitric oxide donor, l-arginine, against liver IR-induced damage. Results Compared to the sham-operated control group, the hepatic IR group displayed a significant increase in serum levels of ALT and AST, plasma levels of MDA and TNF-α, and significant decrease in plasma TAC and nitrite levels together with the worsening of liver histological picture. L-Arg, Oxy, moderate intensity exercise, and the combination of both Oxy and moderate intensity exercises ameliorated these deleterious effects that were evident by the significant decrease in serum levels of ALT and AST, significant elevation in TAC and nitrite, and significant decline in lipid peroxidation (MDA) and TNF-α, besides regression of histopathological score regarding hepatocyte necrosis, vacuolization, and nuclear pyknosis. Both the moderate intensity exercise-trained group and Oxy-treated group showed a significant decline in TNF-α and nitrite levels as compared to l-Arg-treated group. The Oxy-treated group showed statistical insignificant changes in serum levels of ALT, AST, and plasma levels of nitrite, MDA, TAC, and TNF-α as compared to moderate intensity exercise-trained group. Conclusion The combination of both moderate intensity exercise and Oxy displayed more pronounced hepatoprotection on comparison with l-Arg which could be attributed to their more prominent antioxidant and anti-inflammatory effects but not due to their NO-enhancing effect.