The effect of metformin preconditioning on mitochondrial dynamics in a rat model of hepatic ischemia–reperfusion injury

Objective: This study aimed to investigate the effects of metformin preconditioning on mitochondrial dynamics in a rat model of hepatic ischemia-reperfusion injury (HIRI). Methods: Thirty Wistar Albino rats were randomly divided into three groups: Sham, HIRI, and Metformin + HIRI. HIRI was induced by clamping the hepatic pedicle for 45 minutes, followed by 6 hours of reperfusion. The Metformin group received 300 mg/kg of metformin via orogastric gavage once daily for 7 consecutive days prior to surgery. Results: In the HIRI group, liver injury was prominent, with increased levels of ALT, AST, MPO, TNF-α and decreased levels of ATP. Significant improvements were observed in the Metformin + HIRI group (p<0.05). Liver injury was significantly limited by metformin preconditioning. Analysis of mitochondrial dynamic proteins revealed increased Fis1, Drp1 expression and decreased MFN1, MFN2 and OPA1 levels in the HIRI group. These changes were limited following metformin preconditioning. Conclusion: Metformin preconditioning is effective in attenuating HIRI by limiting oxidative stress, inflammation, and mitochondrial dysfunction. These protective effects are associated with the inhibition of mitochondrial fission and promotion of fusion. Metformin may serve as a potential therapeutic agent by regulating mitochondrial dynamics and protecting liver cells against HIRI.