Oligomerized Grape Seed Proanthocyanidins Ameliorates Isoproterenol-induced Cardiac Remodeling in Rats: Role of Oxidative Stress

The effects of oligomerized grape seed proanthocyanidins (GSP) on haemodynamics, cardiac hypertrophy and fibrosis as well as apoptosis signal-regulating kinase 1 (ASK1) and nuclear factor-kappa B (NF-kappa B) cascades in isoproterenol (Iso)-induced cardiac remodelling (CR) rat model were investigated, in addition, the serum SOD activities and MDA content were assayed. Rats were treated with Iso to induce CR and were given distilled water or GSP for 1 week. Control rats received vehicle instead of Iso. Administration of GSP markedly alleviated the elevation of the left ventricle weight (LVW)/body weight (BW), heart weight (HW)/body weight (BW) ratio and cross-sectional area of cardiomyocytes, decreased collagen deposition in the heart, and improved the haemodynamic index. Meanwhile, treatment with GSP significantly ameliorated oxidative stress by improving SOD activities and decreasing MDA formation. Moreover, GSP apparently inhibited the expression ASK1, NF-kappa B and its targeted gene - COX-2. These findings suggest that administration of GSP has the potential to attenuate Iso-induced CR by repressing oxidative stress and inhibiting the activation of the cellular signaling cascades involving the ASK1 and NF-kappa B pathways, at least in part, providing a molecular mechanism for the cardioprotective effect of GSP. Copyright (C) 2010 John Wiley & Sons, Ltd.