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Background: Acute liver injury (ALI) is a critical and fatal disorder which is associated with excessive oxida¬tive stress and inflammation and ultimate death of hepatocytes. Myricetin is a bioflavonoid in some berries including blueberries and strawberries with anti-inflammatory, antioxidant and anti-apoptotic properties. Objective: In the current research, hepatoprotective potential of myricetin was studied in LPS/D-GalN model of ALI in C57BL/6 mice. Methods: For inducing liver injury, D-GalN (400 mg/kg) and LPS (50 g/kg) was injected via intraperitoneal route and myricetin was orally administered (25 or 100 mg/kg/day), from two days till 1 h before inducing injury. Functional indices of liver dysfunction along with hepatic apoptotic, autophagic, oxidative stress and inflammatory factors were measured. Results: Myricetin (100 mg/kg) reduced lethality rate of animals and liver pathological changes and suitably lowered serum levels of total bilirubin, 8-OH-dG, ALT, AST and ALP in addition to decreasing apoptotic, oxidative and inflammatory factors, NOX, NLRP3, caspase 3, MPO and enhancing some antioxidants. Besides, myricetin improved hepatic level and activity of sirtuin 1 and reversed inappropriate alterations of autophagic parameters including LC3 II, Beclin 1 and P62. Beneficial effects of myricetin was attenuated after co-treatment with the autophagy inhibitor 3-methyladenine. Conclusion: This study indicates hepatoprotective potential of myricetin that can be ascribed to its down-regulation of oxidative, apoptotic and inflammatory factors and upregulation of antioxidants besides its partial regulation of sirtuin 1 and autophagic pathway.

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