الملخص

Methotrexate (MTX) is a widely employed chemotherapeutic and immunosuppressive agent, but its clinical use is frequently hampered by hepatotoxic side effects due to oxidative stress and inflammation. The objective of the current study was to investigate the hepatoprotective effects of melatonin and resveratrol, as single agents or in combination, against liver injury induced by methotrexate (MTX) in male rats. Fifty adult male rats were randomly assigned into five groups, including control group, MTX group (20 mg/kg/week), MTX + melatonin group (30 mg/kg/day), MTX + resveratrol group (25 mg/kg/day) and treatment groups in which both melatonin and resveratrol administrated orally. Impressions The changes in liver enzymes, oxidative stress markers, antioxidant parameters, and histopathological alterations were evaluated at the end of the ethanol-feeding period. MTX treatment resulted in profound liver damage as shown by increased serum liver biochemistry parameters and enhanced malondialdehyde levels with concomitant modifications of the antioxidant defense systems. Melatonin or resveratrol treatments ameliorated these negative effects by correcting oxidative balance, enhancing hepatic tissue damage. The combined treatment had a more potent protective effect than single treatments, leading to significant amelioration of biochemical and histopathological outcomes. The study demonstrated that melatonin and resveratrol are potent antioxidants and hepatoprotectors from MTX-induced liver toxicity, but their combination has a higher protective efficacy than each agent when used alone due to synergistic antioxidant activity