Resveratrol alleviates hypoxia/reoxygenation injury-induced mitochondrial oxidative stress in cardiomyocytes

Resveratrol (RES) is a naturally occurring antioxidant compound found in red wine. Although it has been demonstrated to have a cardioprotective effect, the mechanism underlying this effect remains to be fully elucidated. The aim of the present study was to determine whether RES exerts a protective effect against mitochondrial oxidative stress and apoptosis in neonatal rat cardiomyocytes (NRCMs) induced by hypoxia/reoxygenation (H/R) injury. Primary cultured NRCMs were used as a model system and were divided into four experimental groups: Control, H/R, H/R + DMSO (H/R with 0.2% DMSO) and H/R + RES (H/R with 100 mu M RES) groups. Mitochondrial oxidative stress was determined by measuring the alteration in the mitochondrial membrane potential (m) of NRCMs, the release of lactate dehydrogenase (LDH) and the ratio of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) from NRCMs. Cell apoptosis was assessed by measuring cell apoptotic rates and the activity of caspase 3. In the H/R+RES group, RES significantly alleviated structural impairment, including disordered -actin and F-actin, in the NRCMs induced by H/R injury. RES attenuated H/R injury-induced mitochondria oxidative stress. RES also attenuated H/R injury-induced cell apoptosis; it decreased the NRCM apoptotic rate from 84.25 +/- 7.41% (H/R) to 46.39 +/- 5.43% (H/R+RES) (P<0.05, n=4), rescued the decrease in the Bcl2/Bax ratio induced by H/R from 0.53 +/- 0.08-fold (H/R) to 0.86 +/- 0.06-fold (H/R+RES) (P<0.05, n=5) and alleviated the increased activity of caspase 3 induced by H/R from 1.32 +/- 0.06-fold to 1.02 +/- 0.04-fold (P<0.05, n=5). Furthermore, RES significantly attenuated the increment of LDH release induced by H/R injury in NRCMs from 1.41 +/- 0.03-fold (H/R) to 1.02 +/- 0.06-fold (H/R+RES) (P<0.01, n=4) and alleviated the depolarization of m induced by H/R, shifting the ratio of JC-1 monomer from 62.39 +/- 1.82% (H/R) to 35.31 +/- 8.63% (H/R+RES) (P<0.05, n=4). RES alleviated the decrease in sirtuin 1 induced by H/R injury from 0.61 +/- 0.06-fold (H/R) to 1.01 +/- 0.05-fold (H/R+RES) (P<0.05, n=5). In conclusion, the present study is the first, to the best of our knowledge, to demonstrate that RES provides cardioprotection against H/R injury through decreasing mitochondria-mediated oxidative stress injury and structural impairment in NRCMs. These results provide scientific evidence for the clinical application of RES in the treatment of cardiac conditions.