Postconditioning with metformin attenuates apoptotic events in cardiomyoblasts associated with ischemic reperfusion injury.

Aim: Ischemic postconditioning is considered as a potent method to combat ischemic reperfusion injury than preconditioning and rapid initiation of reperfusion with potent antioxidant compounds can be one of the most effective treatments to reduce the infarct size and behavioral deficits as a result of ischemic insult. The present study aims to determine the postconditioning effects of metformin in experimental ischemia.

Methods: H9C2 cells were subjected to experimental ischemia and reperfused with metformin. Viability, oxidative stress and apoptotic events were determined.

Results: Postconditioning with Metformin effectively maintained cell viability and membrane stability of H9C2 cardiomyoblast cells from ischemic injury at a concentration of 2.5 µg/mL. Decrease in cell death was established viz fluorescent staining and Annexin V-FITC flow cytometric analysis. In metformin treated ischemic cells the DNA fragmentation and comet length were significantly reduced (p=.0001) affirming antiapoptotic activity of metformin. There was an increase in protein carbonyl content and decrease in nitrate levels after ischemic injuries which were alleviated with metformin treatment. Wound closure was enhanced by metformin treatment. Metformin synchronized the apoptotic proteins such as FasL and antiapoptotic proteins such as Bcl2, Bcl-xL and p21 which can be attributed as the major mechanism of cardioprotection.

Conclusions: The results envisage therapeutic potential of metformin at lower concentrations as an effective postischemic conditioning agent.