Effects by doxorubicin on the myocardium are mediated by oxygen free radicals.
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 beta-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.
Xu
M F
MF
Department of Pathology and Laboratory Medicine, University of Cincinnati, OH 45267-0529, USA.
Tang
P L
PL
Qian
Z M
ZM
Ashraf
M
M
D000185:Actinin / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000633:toxicity; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D017382:Reactive Oxygen Species; D011943:Receptors, Adrenergic, beta; D000185:Actinin; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D008550:Melatonin