Abstract 19196: Resveratrol Prevents the Oxidative Stress and Diastolic Dysfunction in Iron-overload Cardiomyopathy
Introduction: Iron-overload cardiomyopathy results in heart failure with high morbidity and mortality. Iron-overload results in iron-induced oxidative stress and organ dysfunction and is associated with genetic and acquired iron-overload conditions. Resveratrol is a natural polyphenol with a broad range therapeutic potential.
Hypothesis: We hypothesized that resveratrol will reduce iron-induced oxidative stress and prevent iron-overload cardiomyopathy.
Methods and Results: Iron-overload cardiomyopathy was induced by treating 10 week old male C57Bl6 mice sub-acutely with iron-dextran at 5 mg/25g body weight i.p, 5 days/week for 4 weeks. The antioxidant and metabolic modulator, resveratrol was given at 190 mg/kg/day. Quantification of tissue iron showed significant deposition in the heart (350±27 vs 5304±773 µg/mg tissue; n=10, p<0.01) which was confirmed by Prussian blue staining. Hemodynamic (+dP/dt/-dP/dtmax ratio=1.0 vs 1.7; n=6) and echocardiographic (E/A ratio: 1.46±0.043 vs 1.27±0.06, n=6, p<0.05; E’/A’ ratio: 0.77±0.04 vs 1.20±0.05, n=7, p<0.01) analysis showed diastolic dysfunction with preserved systolic function in iron-overload hearts in the absence of increased myocardial fibrosis. Resveratrol treatment prevented the development of diastolic dysfunction (E/A ratio:1.27±0.06 vs 1.67±0.13 and E’/A’:1.2±0.05 vs 0.80±0.02; n=7, p< 0.01; hemodynamic: +dP/dt/-dP/dt ratio: 1.6 vs 1.1 n=6, p<0.01) without altering the degree of iron-overload (5200±743 µg/mg tissue ; n=10). Increased expression of ANF (65%), BNP (103%) and β-MHC (44%) showed a complete normalization with resveratrol treatment. Expression of oxidative stress-related genes, thioredoxin (91%), catalase (140%), glutathione peroxidase (548%) and superoxide dismutase (87%) were increased in iron-overload mice treated with resveratrol with a complete normalization of reduced glutathione levels in the heart (GSH: 50 vs 250ng/mg tissue).
Conclusions: Iron-overload resulted in oxidative stress mediated selective diastolic dysfunction with preserved systolic function. Treatment with resveratrol can prevent oxidative stress and myocardial injury and protect the heart from the iron-overload induced diastolic dysfunction.
- © 2012 by American Heart Association, Inc.