Melatonin as an effective protector against doxorubicin-induced cardiotoxicity

Am J Physiol Heart Circ Physiol. 2002 Jul;283(1):H254-63. doi: 10.1152/ajpheart.01023.2001.

Abstract

The present study was designed to explore the protective effects of melatonin and its analogs, 6-hydroxymelatonin and 8-methoxy-2-propionamidotetralin, on the survival of doxorubicin-treated mice and on doxorubicin-induced cardiac dysfunction, ultrastructural alterations, and apoptosis in mouse hearts. Whereas 60% of the mice treated with doxorubicin (25 mg/kg ip) died in 5 days, almost all the doxorubicin-treated mice survived when melatonin or 6-hydroxymelatonin (10 mg/l) was administered in their drinking water. Perfusion of mouse hearts with 5 microM doxorubicin for 60 min led to a 50% suppression of heart rate x left ventricular developed pressure and a 50% reduction of coronary flow. Exposure of hearts to 1 microM melatonin or 6-hydroxymelatonin reversed doxorubicin-induced cardiac dysfunction. 8-Methoxy-2-propionamidotetralin had no protective effects on animal survival and on in vitro cardiac function. Infusion of melatonin or 6-hydroxymelatonin (2.5 microg/h) significantly attenuated doxorubicin-induced cardiac dysfunction, ultrastructural alterations, and apoptosis in mouse hearts. Neither melatonin nor 6-hydroxymelatonin compromised the antitumor activity of doxorubicin in cultured PC-3 cells. These results suggest that melatonin protect against doxorubicin-induced cardiotoxicity without interfering with its antitumor effect.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity
  • Apoptosis / drug effects
  • Body Weight / drug effects
  • Cardiotonic Agents / pharmacology*
  • Creatine Kinase / blood
  • Cytoprotection / drug effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / toxicity*
  • Heart / drug effects*
  • Heart / physiopathology
  • Heart Diseases / chemically induced
  • Heart Diseases / pathology
  • Heart Diseases / prevention & control*
  • In Vitro Techniques
  • Lethal Dose 50
  • Male
  • Melatonin / analogs & derivatives*
  • Melatonin / pharmacology*
  • Mice
  • Mice, Inbred ICR
  • Myocardium / pathology
  • Organ Size / drug effects
  • Perfusion
  • Survival Rate
  • Tumor Cells, Cultured
  • Ventricular Function, Left / drug effects

Substances

  • Antineoplastic Agents
  • Cardiotonic Agents
  • Doxorubicin
  • Creatine Kinase
  • Melatonin
  • 6-hydroxymelatonin