Metformin ameliorates hypoxia/reoxygenation-induced cardiomyocyte apoptosis based on the SIRT3 signaling pathway.

Myocardial hypoxia/reoxygenation (H/R) injury is one of the main causes of death and disability worldwide. However, a limited number of therapies are available to minimize the detrimental effects of this injury. Recently, researchers have demonstrated that metformin exerts direct cardioprotective effects against H/R. The aim of this study was to investigate the underlying mechanisms of how metformin affects myocardial hypoxia/reoxygenation (H/R) injury. In our study, the activities of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) as well as the levels of malondialdehyde (MDA) were measured. Following H/R injury, LDH activity and MDA levels were evidently increased, while SOD activity and cell viability significantly decreased. Surprisingly, metformin downregulated the levels of relative reactive oxygen species (ROS) and upregulated the levels of relative SOD following H/R injury. Furthermore, metformin-treated cells exhibited reduced cell death, which was demonstrated to be associated with increased SIRT3 expression compared to that in the control group, as evidenced by blocking of the protective effects of metformin on cell apoptosis by the SIRT3 inhibitor Nicotinamide (NAM). Therefore, our results demonstrate that metformin improves cells viability following H/R, and this cardioprotective effect is partly mediated by the SIRT3 signaling pathway.