Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: a possible mechanism of protection

Pharmacol Res. 2000 Mar;41(3):283-9. doi: 10.1006/phrs.1999.0585.

Abstract

Administration of thymoquinone (10 mg kg(-1)day(-1), p.o.) with drinking water starting 5 days before a single injection of doxorubicin (15 mg kg(-1)i.p.) and continuing during the experimental period ameliorated the doxorubicin-induced cardiotoxicity in rats. This protection was evidenced from the significant reduction in serum enzymes: lactate dehydrogenase elevated level, 24 h and creatine phosphokinase elevated levels, 24 h and 48 h after doxorubicin administration. The cardiotoxicity of doxorubicin has been suggested to result from the generation of superoxide free-radical. The protective action of thymoquinone was examined against superoxide anion radical either generated photochemically, biochemically or derived from calcium ionophore (A23187) stimulated polymorphonuclear leukocytes. The results indicate that thymoquinone is a potent superoxide radical scavenger, scavenging power being as effective as superoxide dismutase against superoxide. In addition thymoquinone has an inhibitory effect on lipid peroxidation induced by Fe(3+)/ascorbate using rat heart homogenate. The superoxide scavenging and anti-lipid peroxidation may explain, in part, the protective effect of thymoquinone against doxorubicin-induced cardiotoxicity. 2000 Academic Press@p$hr

MeSH terms

  • Animals
  • Ascorbic Acid / pharmacology
  • Benzoquinones / pharmacology*
  • Creatine Kinase / drug effects
  • Creatine Kinase / metabolism
  • Doxorubicin / adverse effects*
  • Drug Interactions
  • Enzyme Activation / drug effects
  • Ferric Compounds / pharmacology
  • Free Radical Scavengers / pharmacology*
  • Heart / drug effects*
  • Heart Rate / drug effects
  • L-Lactate Dehydrogenase / drug effects
  • L-Lactate Dehydrogenase / metabolism
  • Lipid Peroxidation / drug effects
  • Male
  • Protective Agents / pharmacology*
  • Rats
  • Superoxides / metabolism

Substances

  • Benzoquinones
  • Ferric Compounds
  • Free Radical Scavengers
  • Protective Agents
  • Superoxides
  • Doxorubicin
  • L-Lactate Dehydrogenase
  • Creatine Kinase
  • thymoquinone
  • Ascorbic Acid