Abstract P2007: Muscadine Grape Extract Prevents Cardiac Cell Cytotoxicity Due to Oxidative Stress by Enhancing Mitochondrial Function

Abstract

Mitochondrial health is critical for the physiological function of tissues and responses to stress. During oxidative stress, failure to maintain mitochondrial respiration can ultimately lead to cell death and thus cardiac dysfunction. Agents that preserve mitochondrial integrity and maintain or increase mitochondrial respiratory capacity may prevent cardiac tissue damage due to oxidative stress. Muscadine grapes are rich in polyphenols, which are natural antioxidants, and are known to reduce cardiac damage. We treated cardiac cells with a proprietary muscadine grape extract (MGE), to prevent cardiac myoblast death due to reactive oxygen species (ROS) in the presence of the redox cycling agent 2,3 dimethoxynaphthoquinone (DMNQ), which generates both superoxide and hydrogen peroxide intracellularly, thus mimicking pathologies of elevated ROS. DMNQ increased cardiac cell cytotoxicity, as measured by LDH release, which was prevented by doses of MGE equivalent to 60 μg/mL of total phenolics (1.3 ± 0.023 DMNQ vs. 0.90 ± 0.030, n=3, *p<0.01). Moreover, cell respirometry measurements indicated that, while DMNQ reduced the oxygen consumption rate (OCR) by 50% (*p<0.05, n=3), treatment with MGE prevented this reduction, suggesting that the protective effect may be mediated by preservation of mitochondrial function. Furthermore, MGE treatment prevented the decrease in ATP-linked respiration (18.8 ±. 2.6 DMNQ vs. 34.0±.4.7 DMNQ + MGE, n=3, *p<0.01) and maximal respiratory capacity (31.6 ± 8.2 DMNQ vs. 48.91 ± 6.54 DMNQ + MGE, n=3, *p<0.01) observed with DMNQ treatment. Furthermore, the basal extracellular acidification rate (ECAR) was increased 2-fold with MGE pretreatment when compared to DMNQ alone (13.6 ± 2.3 DMNQ + MGE vs. 6.8 ±.0.88 DMNQ, n=3, *p<0.01), suggesting that MGE treatment may also increase glycolysis as a response to stress. These data suggest that MGE enhances mitochondrial function and cellular bioenergetics in cardiomyoblast cells during stress and thus may be used as a strategy to prevent tissue damage from oxidative stress observed in acute and chronic cardiac pathologies.