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Doxorubicin cardiotoxicity: analysis of prevailing hypotheses
Author(s) -
Olson Richard D.,
Mushlin Phillip S.
Publication year - 1990
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.4.13.2210154
Subject(s) - cardiotoxicity , doxorubicin , anthracycline , daunorubicin , pharmacology , cardiomyopathy , chemistry , medicine , heart failure , toxicity , chemotherapy , cancer , breast cancer
Anthracyclines, such as doxorubicin and daunorubicin, are highly effective anticancer agents that produce a well‐described but incompletely understood cardiac toxicity. According to a popular hypothesis, anthracyclines injure the heart by generating oxygen‐centered free radicals. This free radical hypothesis, however, appears to be inconsistent with many observations, such as the frequent failure of anthracyclines at cardiotoxic doses to produce evidence of increased free radical generation. Other explanations of cardiotoxicity involve platelet‐activating factor, prostaglandins, histamine, calcium, and C‐13 hydroxy anthracycline metabolites. These C‐13 hydroxy metabolites, on the basis of in vitro data, are considerably more potent than parent compounds as myocardial depressants and as inhibitors of ATPases of sarcoplasmic reticulum, mitochondria, and sarcolemma. Further studies will be required to determine whether metabolites or the other putative injurious agents discussed contribute substantially to the cardiomyopathy of anthracycline therapy. The hypotheses presented in this paper should provide a useful framework for subsequent investigations into the mechanisms of anthracycline cardiotoxicity.— O lson , R. D.; M ushlin , P. S. Doxorubicin cardiotoxicity: analysis of prevailing hypotheses. FASEB J. 4: 3076‐3086; 1990.