Nebivolol and chrysin protect the liver against ischemia/reperfusion-induced injury in rats

Abstract

Oxidative stress plays a key role in the pathogenesis of hepatic ischemia/reperfusion (I/R)-induced injury, one of the leading causes of liver damage post-surgical intervention, trauma and transplantation. This study aimed to evaluate the protective effect of nebivolol and chrysin against I/R-induced liver injury via their vasodilator and antioxidant effects, respectively. Adult male Wister rats received nebivolol (5 mg/kg) and/or chrysin (25 mg/kg) by oral gavage daily for one week then subjected to ischemia via clamping the portal triad for 30 min then reperfusion for 30 min. Liver function enzymes, alanine transaminase (ALT) and aspartate transaminase (AST), as well as hepatic Myeloperoxidase (MPO), total nitrate (NOx), glutathione (GSH) and liver malondialdehyde (MDA) were measured at the end of the experiment. 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 and confirmed by immunohistochemical analysis. Both chrysin and nebivolol significantly counteracted I/R-induced oxidative stress and tissue damage biomarkers. The combination of these agents caused additive liver protective effect against I/R-induced damage via the up regulation of nitric oxide expression and the suppression of oxidative stress. Chrysin and nebivolol combination showed a promising protective effect against I/R-induced liver injury, at least in part, via decreasing oxidative stress and increasing nitric oxide levels.

Keywords

• Ischemia-reperfusion
• Nitric oxide synthetase
• Nebivolol
• Chrysin
• Liver injury
• Oxidative stress