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 journalArticle

123 Citations (Scopus)

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

Fingerprint

Doxorubicin
Free Radicals
Reactive Oxygen Species
Myocardium
Oxygen
Melatonin
Muscle Cells
Rats
Antioxidants
Membranes
Myofibrils
Cell membranes
Adrenergic Receptors
Hydrogen Peroxide
Lipid Peroxidation
Actins
Permeability
Cell Membrane
Lipids
Enzymes

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)

Cite this

Effects by doxorubicin on the myocardium are mediated by oxygen free radicals. / Xu, Mei Feng; Tang, Pak Lai; Qian, Zhong Ming; Ashraf, Muhammad.

In: Life sciences, Vol. 68, No. 8, 12.01.2001, p. 889-901.

Research output: Contribution to journalArticle

Xu, Mei Feng ; Tang, Pak Lai ; Qian, Zhong Ming ; Ashraf, Muhammad. / Effects by doxorubicin on the myocardium are mediated by oxygen free radicals. In: Life sciences. 2001 ; Vol. 68, No. 8. pp. 889-901.
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