Resveratrol protects adult cardiomyocytes against oxidative stress mediated cell injury

Recent studies from our laboratory have showed that resveratrol, a polyphenol found predominantly in grapes rendered strong cardioprotection in animal models of heart disease. The cardioprotection which was observed was primarily associated with the ability of resveratrol to reduce oxidative stress in these models. The aim of the current study was to corroborate the role of resveratrol as an inhibitor of oxidative stress and explore the underlying mechanisms of its action in heart disease. For this purpose, we used a cell model of oxidative stress, the hydrogen peroxide (H2O2) exposed adult rat cardiomyocytes, which was treated with and without resveratrol (30 mu M); cardiomyocytes which were not exposed to resveratrol served as controls. Cell injury, cell death and oxidative stress measurements as well as the activities of the major endogenous antioxidants superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were carried out in control and H2O2 exposed cardiomyocytes, treated with and without resveratrol. Pharmacological blockade using specific blockers of the antioxidant enzymes were used to confirm their role in mediating resveratrol action in H2O2 exposed cardiomyocytes. The status of H2O2 and antioxidant enzymes in serum samples from spontaneously hypertensive rats (SHR) treated with and without resveratrol (2.5 mg/kg body weight) was also examined. Our results showed significant cell injury and death in H2O2 exposed cardiomyocytes which was prevented upon resveratrol treatment. SOD and CAT activities were decreased in H2O2 exposed adult rat cardiomyocytes; treatment with resveratrol significantly prevented this reduction. However, GPx activity was not altered in the H2O2 exposed cardiomyocytes in comparison to controls. Pharmacological blockade of SOD and/or CAT prevented the beneficial effect of resveratrol. In SHR, H2O2 levels were increased, but CAT activity was decreased, while SOD remained unchanged, when compared to WKY rats; resveratrol treatment significantly prevented the increase in H2O2 levels and the decrease in CAT activities in SHR. Based on our results, we conclude that treatment with resveratrol prevents oxidative stress induced cardiomyocyte injury mainly by preserving the activities of critical antioxidant enzymes. This may be a crucial mechanism by which resveratrol confers cardioprotection. (C) 2012 Elsevier Inc. All rights reserved.