The Cardioprotective Effects of Resveratrol via Anti-Apoptosis in Hypoxic Injury of Myocardial Cells

Abstract

Background and Objectives：Resveratrol (trans-3, 4', 5-trihydroxy-stilbene), a naturally occurring polyphenolic phytoalexin found abundantly in grape skins and red wines, has been reported to protect heart cells from ischemia/ reperfusion (I/R) injury through its significant antioxidant properties. Apoptosis of cardiac myocytes is also involved in several cardiovascular diseases, but it remains unknown whether the protective effects of resveratrol in hypoxic myocardial cell injury are mediated via suppression of apoptosis. In this study, we investigated whether resveratrol confers cardioprotection against hypoxia via anti-apoptosis in a hypoxic model of cultured H9c2 cardiomyoblasts. Materials and Methods：H9c2 cardiomyoblasts were obtained from the Korean Cell Line Bank. The cultured cells were divided into four groups: a normal control group, a hypoxia group, a group treated with resveratrol (10 μg/mL) before hypoxic insult, and a group treated with resveratrol (10 μg/mL) after hypoxic insult. The control group was placed in 5% CO 2 incubators, and the hypoxia and resveratrol-treated groups were placed in 1% O 2 incubators. Apoptosis was assayed by cytological analysis with Western blotting and real-time PCR for Bcl-2, Bax, and caspase-3. Results：The expression of Bcl-2 was significantly decreased in the hypoxia group compared with the control group, and resveratrol treatment inhibited the hypoxia-induced decline of Bcl-2 in hypoxic myocardial cells. Conversely, the expressions of Bax and caspase-3 were significantly increased in the hypoxia group, while resveratrol inhibited the hypoxia-induced increase of Bax and caspase. In addition, hypoxia significantly increased the ratio of Bax/Bcl-2 expression, but it was significantly decreased in the resveratrol-treated group. Conclusion：The present study demonstrates that the cardioprotective effects of resveratrol in hypoxic injury are mediated via the mechanisms of antiapoptosis. (Korean Circulation J 2007;37: [408][409][410][411][412][413]

Prophylactic supplementation of resveratrol is more effective than its therapeutic use against doxorubicin induced cardiotoxicity

“…Also RSV administration exerted cardioprotective effects by reducing oxidative stress in a rat model of diabetic cardiomyopathy [ 16 ]. Similarly, RSV inhibited hypoxia-induced apoptosis in myocardial cells by preventing an increase in Bax and caspase 3 activation [ 17 – 20 ]. Resveratrol also prevents Dox-induced cardiotoxicity by mitigating cardiomyocyte apoptosis, oxidative stress and cardiac fibrosis [ 21 – 23 ].…”

Cardioprotective Effects of Alpha-Lipoic Acid on Myocardial Reperfusion Injury: Suppression of Reactive Oxygen Species Generation and Activation of Mitogen-Activated Protein Kinase

“…However, ROS are formed in excessive amounts within the first few minutes following reperfusion and are considered a major factor involved in myocardial reperfusion injury 5)21-23). To minimize reperfusion injury, powerful antioxidants have been administered to reduce ROS generation and thereby decrease myocardial injury 17)24)25). Among the antioxidants, ALA, a thiol compound, is a cofactor for mitochondrial dehydration enzymes.…”

“…5) 21 - 23) To minimize reperfusion injury, powerful antioxidants have been administered to reduce ROS generation and thereby decrease myocardial injury. 17) 24) 25) Among the antioxidants, ALA, a thiol compound, is a cofactor for mitochondrial dehydration enzymes. In the tissue mitochondria, it is reduced to dithiol dihydrolipoic acid (DHLA), an effective form.…”

Preventive Effects of Resveratrol against Beta Adrenergic Catecholamine –Induced Acute Myocardial Stress during Experimental Hyperglycemia in in vivo and in vitro Models

“…On arriving at confluency, the cells (5 X 10 6 cells/ml) were plated on to 96 well microtiter plate. The cells were allowed to attach overnight and then pretreated with resveratrol (30µg/ml for 30 minutes) [25,26]. Following this, experimental hyperglycemic conditions were induced in H9 c2 cells by exposing them to high concentration of glucose (30 mM/L) [27] for 24 hours.…”