Protective role of atorvastatin against doxorubicin-induced cardiotoxicity and testicular toxicity in mice

J Physiol Biochem. 2013 Sep;69(3):513-25. doi: 10.1007/s13105-013-0240-0. Epub 2013 Feb 6.

Abstract

Doxorubicin (DOX), a potent chemotherapeutic agent, is widely used for the treatment of various malignancies. However, its clinical uses are limited due to its dose-dependent adverse effects particularly cardiac and testicular toxicities. DOX-induced toxicity is mainly due to the induction of oxidative stress. Atorvastatin (ATV), a 3-hydroxy 3-methyl glutaryl coenzyme A reductase inhibitor, with lipid-lowering activity, acts as an antioxidant at lower doses. It possesses pleiotropic effects independent of cholesterol-lowering property usually shown at lower doses, which include antioxidant and anti-inflammatory activities. The present study was aimed to investigate the possible protection exerted by atorvastatin against oxidative stress and DNA damage induced by DOX in the heart and testes of mice. The protective role of ATV in the heart and testes of DOX-treated mice was evident from the amelioration of oxidative stress, DNA and cellular damage. The present study clearly indicates that ATV offers a significant protection against DOX-induced oxidative stress and DNA damage in the heart and testes of mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Atorvastatin
  • Cardiomyopathies / chemically induced
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / prevention & control*
  • Comet Assay
  • DNA Fragmentation / drug effects
  • Doxorubicin
  • Glutathione / metabolism
  • Heart / drug effects*
  • Heptanoic Acids / pharmacology*
  • Lipid Peroxidation / drug effects
  • Male
  • Malondialdehyde / metabolism
  • Mice
  • Micronucleus Tests
  • Oxidative Stress / drug effects
  • Pyrroles / pharmacology*
  • Testicular Diseases / chemically induced
  • Testicular Diseases / metabolism
  • Testicular Diseases / prevention & control*
  • Testis / drug effects
  • Testis / metabolism*

Substances

  • Antioxidants
  • Heptanoic Acids
  • Pyrroles
  • Malondialdehyde
  • Doxorubicin
  • Atorvastatin
  • Glutathione