Doxorubicin-induced cardiac mitochondrionopathy

Research output: Contribution to journalShort survey

269 Citations (Scopus)

Abstract

Doxorubicin (Adriamycin®) is a potent and broad-spectrum antineoplastic agent prescribed for the treatment of a variety of cancers, including both solid tumours and leukaemias. Unfortunately, despite its broad effectiveness, long-term therapy with doxorubicin is associated with a high incidence of a cumulative and irreversible dilated cardiomyopathy. Numerous mechanisms have been proposed to account for this toxicity. Although there is general consensus that doxorubicin undergoes redox cycling to generate free radicals that are responsible for mediating the various cytopathologies associated with drug exposure, the source and subcellular targets continue to be debated. This short review provides a synopsis of the evidence implicating cardiac mitochondria as key intracellular targets, both as sites of generation of highly reactive free radical intermediates as well as targets for the interference with cell calcium regulation and bioenergetic failure that are hallmarks of doxorubicin-induced cardiac failure.

Original languageEnglish (US)
Pages (from-to)105-115
Number of pages11
JournalPharmacology and Toxicology
Volume93
Issue number3
DOIs
StatePublished - Sep 1 2003

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Doxorubicin
Free Radicals
Mitochondria
Dilated Cardiomyopathy
Antineoplastic Agents
Energy Metabolism
Oxidation-Reduction
Toxicity
Tumors
Neoplasms
Leukemia
Heart Failure
Calcium
Incidence
Pharmaceutical Preparations
Therapeutics

Cite this

Doxorubicin-induced cardiac mitochondrionopathy. / Wallace, Kendall B.

In: Pharmacology and Toxicology, Vol. 93, No. 3, 01.09.2003, p. 105-115.

Research output: Contribution to journalShort survey

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