Adriamycin-induced heart failure: mechanism and modulation.
Adriamycin (doxorubicin) is one of the most effective chemotherapeutic agents against a variety of cancers, but its usefulness is seriously curtailed by the risk of developing heart failure. Available laboratory evidence suggests that an increase in oxidative stress, brought about by increased free radical production and decreased myocardial endogenous antioxidants, plays an important role in the pathogenesis of heart failure. Adriamycin-induced apoptosis and hyperlipidemia may also be involved in the process. Probucol, a lipid-lowering drug and an antioxidant, completely prevents the occurrence of heart failure by reducing oxidative stress as well as by the modulation of apoptosis and high lipid concentrations. Thus, combined therapy with adriamycin and probucol has a high potential for optimizing the treatment of cancer patients.
Singal
P K
PK
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Li
T
T
Kumar
D
D
Danelisen
I
I
Iliskovic
N
N
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D017209:Apoptosis; D004317:Doxorubicin / Q000009:adverse effects* / Q000494:pharmacology; D004359:Drug Therapy, Combination; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000139:chemically induced* / Q000517:prevention & control; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000097:blood; D011341:Probucol / Q000627:therapeutic use
D000924:Anticholesteremic Agents; D000970:Antineoplastic Agents; D008055:Lipids; D004317:Doxorubicin; D011341:Probucol