P497Protective effect of resveratrol against doxorubicin-induced cardiac toxicity and fibrosis in experimental rats

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Objectives: The possible effectiveness of resveratrol, a polyphenol found predominantly in grapes, administration on doxorubicin-induced cardiac toxicity and fibrosis was investigated.

Methods: Fourty adult male Wistar albino rats were divided into four groups. Group I: received normal saline; Group II: gavaged with resveratrol (20 mg/kg, daily for 4 weeks); Group III: received doxorubicin (2.5 mg/kg i.p in 6 injections for 2 weeks; accumulative dose 15 mg/kg); Group IV: received doxorubicin+resveratrol (starting resveratrol intake two weeks before doxorubicin administration).

Key Findings: Resveratrol significantly reduced left ventricular lipid peroxidation, hydroxyproline and tumor necrosis factor-alpha levels, sharply diminished serum creatine kinase-MB activity and prevented the decrease in heart weight in doxorubicin-treated group. However, a significant elevation in reduced glutathione content and superoxide dismutase activity was observed in the left ventricles of rats treated with resveratrol in combination with doxorubicin. Resveratrol also down-regulated left ventricular caspase-3 and transforming growth factor-beta1 gene expression and left ventricular histopathological changes including necrosis and fibrosis induced by doxorubicin.

Conclusions: Collectively, our results suggest that resveratrol provides a significant protection against doxorubicin-induced cardiotoxicity and fibrosis in rats. Therefore, it can be used successfully as a cardioprotective agent in patients treated with doxorubicin due to malignant diseases.

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