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

Abstract

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. | Parameter Group | Normal control | RES | DOX | DOX+RES | |:--------------------- | -------------- | ---------- | ------------- | ------------ | | Heart weight (g) | 1.02±0.11 | 1.04±0.08 | 0.64±0.07# | 0.85±0.08*a | | MDA (nmol/g tissue) | 39.67±4.53 | 37.94±4.08 | 110.41±10.43# | 71.15±6.59*a | | GSH (mmol/g tissue) | 3.92±0.46 | 4.14±0.47 | 1.35±0.12# | 2.85±0.32*a | | SOD (U/mg protein) | 15.54±1.59 | 16.6±1.64 | 8.31±0.75# | 11.85±1.35*a | | Hyp (µg/g tissue) | 38.9±4.01 | 36.85±3.99 | 105.61±13.13# | 75.67±9.02*a | | TNF-α (pg/mg protein) | 2.09±0.2 | 1.93±0.15 | 12.22±1.12# | 4.25±0.39*a | * DOX 15 mg/kg (i.p, accumulative dose); RES 20 mg/kg (P.O.); MDA, malondialdehyde; GSH, reduced glutathione; SOD, superoxide dismutase; TNF-α, tumor necrosis factor-alpha; RES, resveratrol supplemented group; DOX, Doxorubicin-treated group. The values are means ± SD (n = 8). #P < 0.0001 vs normal control, *P < 0.0001 vs DOX, a P < 0.001 vs RES. Resveratrol Supplementation Effects