Effects by doxorubicin on the myocardium are mediated by oxygen free radicals

Mei Feng Xu, Pak Lai Tang, Zhong Ming Qian, Muhammad Ashraf

Research output: Contribution to journalArticlepeer-review

129 Scopus citations

Abstract

We hypothesized that doxorubicin (DOX) induces cardiotoxicity of myocardium via oxygen radicals. The present study is aimed at examining the membrane alterations by oxygen radicals generated by DOX in adult rats and cultured neonatal myocytes. Our results showed that DOX 1) decreased β-adrenoceptor (BAR) density in the cell membrane, 2) increased the membrane permeability of cultured neonatal rat myocytes and 3) altered the ultrastructure of myofibrils and subplasmalemmal actin networks. These effects were reproducible by exogenous hydrogen peroxide. The antioxidant melatonin (MLT) inhibited enzyme leakage and peroxidation in a concentration-dependent manner. It is concluded that DOX induces cardiotoxicity through lipid peroxidation and melatonin is an effective antioxidant against the reactive oxygen intermediates generated by DOX.

Original languageEnglish (US)
Pages (from-to)889-901
Number of pages13
JournalLife sciences
Volume68
Issue number8
DOIs
StatePublished - Jan 12 2001
Externally publishedYes

Keywords

  • Doxorubicin
  • Lipid Peroxidation
  • Melatonin
  • Membrane Permeability
  • Reactive Oxygen Species
  • β-Adrenergic Receptor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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