Combination therapy with probucol prevents adriamycin-induced cardiomyopathy.
Adriamycin (doxorubicin) is a broad spectrum anti-tumor antibiotic used to treat cancer patients. However, the potential usefulness of this drug is currently limited by the development of a dose-dependent cardiomyopathic process terminating in severe heart failure. Although several mechanisms have been suggested to explain the pathogenesis of adriamycin-induced cardiomyopathy, free-radical induced oxidative stress appears to play an important role. A concise description of adriamycin-induced cardiomyopathy is provided. Various combination therapies which have been attempted in the past to modulate the adriamycin-induced cardiomyopathy are also discussed. Recently, it has been discovered that probucol, a lipid lowering agent and potent antioxidant, provides complete protection against adriamycin-induced cardiomyopathy in rats without interfering with the anti-tumor properties of this antibiotic. Clinical trials employing adriamycin therapy in combination with probucol are needed to determine the applied value of these laboratory findings.
Singal
P K
PK
Department of Physiology, University of Manitoba, Winnipeg, Canada.
Siveski-Iliskovic
N
N
Hill
M
M
Thomas
T P
TP
Li
T
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D004317:Doxorubicin / Q000009:adverse effects* / Q000494:pharmacology; D004359:Drug Therapy, Combination; D016166:Free Radical Scavengers / Q000494:pharmacology; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D015227:Lipid Peroxidation; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy; D011341:Probucol / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000009:adverse effects
D000975:Antioxidants; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D011341:Probucol