Metformin and Resveratrol Suppress Oxidative Stress/Hypoxia Axis Associated with the Amelioration of Thioacetamide-Induced Liver Injury

Background and Objective: Chronic liver disease is a serious and often life-threatening condition.The hypothesis is that a combination of metformin and resveratrol could effectively mitigate hepatic injury induced by the hepatotoxic chemical, thioacetamide (TAA), by inhibiting liver tissue levels of the oxidative stress (ROS)/Hypoxia-Inducible Factor 1-alpha (HIF-1") axis were tested.Materials and Methods: To this end, chronic liver injury was induced in rats by TAA (200 mg kgG 1 ) injections for 8 weeks starting at week 2 (model group).Another group was treated with metformin (200 mg kgG 1 ) plus resveratrol (20 mg kgG 1 ) for 2 weeks before TAA injections and continued receiving these agents and TAA until being sacrificed at the end of the experiment, at week 10 (protective group).Results: The model group (TAA) exhibited extensive liver tissue damage associated with a significant (p<0.0001)increase in hepatic tissue levels of ROS/HIF-1", as well as blood and tissue levels of chronic liver injury biomarkers.However, treatment with Met+Res significantly (p<0.0001)effectively inhibited all these parameters.Additionally, a significant (p<0.0001)correlation between hepatocyte damage and tissue and blood levels of ROS, HIF-1", ALT, AST and CRP was observed.Conclusion: The TAA-induced chronic liver injury is associated with an increase in the ROS/HIF-1" axis and biomarkers of hepatic damage, which can be protected for a period of ten weeks by treatment with metformin plus resveratrol.These findings suggest that this combination may have therapeutic potential in humans.