The objective of this study was to evaluate the hepatoprotective effects of resveratrol (RSV) and gamma-glutamylcysteine (γ-GC) against liver damage induced by azathioprine (AZA), with potential implications for combining these compounds with immunosuppressive therapies. The study lasted for 4 weeks and included 50 male Wistar albino rats divided into five groups: a control group treated with normal saline, an AZA group given AZA at 10 mg/kg orally, an RSV group treated with both AZA and RSV (8 ml/kg via IP injection), a γ-GC group receiving AZA and γ-GC (100 mg/kg orally), and a combination group treated with both AZA, RSV (8 ml/kg IP), and γ-GC (100 mg/kg) after a 2-hour interval for 4 weeks. The findings show that AZA administration led to elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), decreased activities of antioxidant enzymes (catalase and superoxide dismutase), and decreased hepatic microRNA-122 (miR-122), markers associated with liver injury. Treatment with RSV and/or γ-GC either separately or together significantly restored liver enzyme levels and improved hepatic tissue health. Furthermore, γ-GC effectively reduced histopathological liver injury in the rats. These results suggest that co-administration of RSV and/or γ-GC provides protective benefits against the hepatotoxic effects of immunosuppressive drugs such as AZA.
