Metformin ameliorates blunted cardioprotective response of ischemic postconditioning in rats subjected to high fat diet

HFD animal showed significant rise in serum total cholesterol and nitrate levels reflecting hypercholesterolaemia and ED. I/R produced significant myocardial damage indicated by an increase in infarct size, specific biomarkers (LDH, CK-MB, cTn I), oxidative stress- inflammatory parameters (heart Nrf-2, TBARS, TNF-α and decreased GSH and catalase levels) and altered hemodynamic index. iPoCo significantly alleviated I/R induced myocardial injury with respect to above parameters in normal rats but failed to produce such an effect in HFD rats. Treatment of metformin (25 µM and 50 µM) not only mimicked the cardioprotective effect of iPoCo in normal rats but also restored the lost effect of iPoCo in HFD rats.