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

J Physiol Biochem. 2014 Sep;70(3):701-11. doi: 10.1007/s13105-014-0339-y. Epub 2014 Jun 18.


The possible effectiveness of resveratrol, a polyphenol present in different plants comprising berries, grapes and peanuts, on the prevention of doxorubicin-induced cardiac toxicity and fibrosis was investigated. Forty 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 six injections for 2 weeks; accumulative dose of 15 mg/kg), and group IV received doxorubicin + resveratrol (starting resveratrol intake 2 weeks before doxorubicin administration). Resveratrol significantly alleviated the increase in left ventricular lipid peroxidation, hydroxyproline, and tumor necrosis factor alpha levels as well as serum creatine kinase-myocardial band (CK-MB) activity and prevented the decrease in body and heart weights in doxorubicin-treated group. However, a marked protection against reduced glutathione content depletion and superoxide dismutase activity reduction was observed in the left ventricles of rats pretreated with resveratrol in combination with doxorubicin. Resveratrol also ameliorated the up-regulation of left ventricular caspase-3 and transforming growth factor-beta1 gene expression as well as left ventricular histopathological changes including necrosis and fibrosis induced by doxorubicin. Collectively, our results suggest that resveratrol provides a significant protection against doxorubicin-induced cardiotoxicity and fibrosis in rats. Therefore, it may be used as a promising cardioprotective agent in patients treated with doxorubicin due to malignant diseases. So, further clinical trials are required to confirm these findings.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Cardiotonic Agents / pharmacology*
  • Cardiotoxicity / metabolism
  • Cardiotoxicity / pathology
  • Cardiotoxicity / prevention & control
  • Caspase 3 / genetics
  • Doxorubicin / antagonists & inhibitors*
  • Doxorubicin / toxicity*
  • Fibrosis
  • Gene Expression / drug effects
  • Glutathione / metabolism
  • Heart / drug effects*
  • Heart Ventricles / drug effects
  • Heart Ventricles / metabolism
  • Heart Ventricles / pathology
  • Male
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Resveratrol
  • Stilbenes / pharmacology*
  • Superoxide Dismutase / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Ventricular Remodeling / drug effects


  • Antioxidants
  • Cardiotonic Agents
  • RNA, Messenger
  • Stilbenes
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta1
  • Doxorubicin
  • Superoxide Dismutase
  • Casp3 protein, rat
  • Caspase 3
  • Glutathione
  • Resveratrol