Antioxidant, antiapoptotic, and antifibrotic effects of the combination of liposomal resveratrol and carvedilol against doxorubicin-induced cardiomyopathy in rats

J Biochem Mol Toxicol. 2020 Jul;34(7):e22492. doi: 10.1002/jbt.22492. Epub 2020 Mar 15.

Abstract

The use of the cytotoxic antibiotic doxorubicin (DOXR) is limited by its dose-dependent cardiotoxicity. The aim of this study was to evaluate the cardioprotective effect of the combination of carvedilol (CARD) and liposomal resveratrol (LIPO RESV) against DOXR-induced cardiomyopathy in rats. The results of the present study showed that DOXR administration significantly increased heart weight/body weight ratio by 35.6%, creatine kinase-MB (CK-MB) by 40.6%, troponin-I levels by 85%, and decreased reduced glutathione level and superoxide dismutase activity by 47% and 52%, respectively compared to the control group. Moreover, cardiac caspase-3 protein expression was upregulated by 51.6% vs the control group. In contrast, treatment of DOXR-administered rats with CARD, RESV, or LIPO RESV and their combination for 6 weeks improved all the above-mentioned measured parameters. In conclusion, concomitant administration of CARD and LIPO RESV exerted additive pharmacological effects in some measured parameters against DOXR-induced cardiomyopathy and this may be a useful cardioprotective strategy.

Keywords: cardiomyopathy; carvedilol; doxorubicin; liposomal resveratrol; resveratrol.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / adverse effects*
  • Antioxidants / administration & dosage*
  • Apoptosis / drug effects*
  • Cardiomyopathies / chemically induced*
  • Cardiomyopathies / drug therapy*
  • Cardiotoxicity / drug therapy
  • Carvedilol / administration & dosage*
  • Caspase 3 / metabolism
  • Doxorubicin / adverse effects*
  • Drug Therapy, Combination
  • Heart / drug effects
  • Liposomes
  • Male
  • Myocardium / metabolism
  • NF-kappa B / metabolism
  • Rats
  • Rats, Wistar
  • Resveratrol / administration & dosage*
  • Signal Transduction / drug effects*
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Antibiotics, Antineoplastic
  • Antioxidants
  • Liposomes
  • NF-kappa B
  • Transforming Growth Factor beta1
  • Carvedilol
  • Doxorubicin
  • CASP3 protein, human
  • Caspase 3
  • Resveratrol