Molecular biology of doxorubicin-induced cardiomyopathy
| Authors | |
|---|---|
| Year of publication | 2002 |
| Type | Article in Periodical |
| Magazine / Source | Experimental and Clinical Cardiology |
| MU Faculty or unit | |
| Citation | |
| Field | Genetics and molecular biology |
| Keywords | doxorubicin; cardiomyopathy; DNA damage; mitochondrial dysfunction; cardioprotection |
| Description | A severe, cumulative, dose-dependent chronic cardiac toxicity is the major limitation of anthracycline therapy. Chronic cardiotoxicity occurs in patients after prolonged administration of Dox; a similar cardiotoxicity can be elicited in many animal species, including the mouse, the rat, the rabbit, the dog , and the monkey, after treatment with Dox. The cardiotoxicity consists of a chronic, progressive cardiomyopathy with myocyte vacuolation and degeneration, interstitial edema, and fibroplasia leading to congestive haert failure. Despite considerable work on the subject, the pathogenesis of the doxorubicin-induced cardiomyopathy is not well understood. However, Dox has been shown to exert a multiplicity of complex biochemical effects on the myocardium, including the following: binding to DNA and alteration of nucleic acids and protein synthesis, lipid peroxidation subsequent to free radical generation, release of histamine and catecholamines, damage to mitochondria, an effect on various cellular membranes, an excess calcium influx, and an effect on collagen matrix. A combination of these effects probably triggers the myocardial lesion. |
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