Abstract
The cumulative cardiac toxicity of the anthracycline antibiotics and their propensity to produce severe tissue injury following extravasation from a peripheral vein during intravenous administration remain significant problems in clinical oncologic practice. Understanding of the free radical metabolism of these drugs and their interactions with iron proteins led to the development of dexrazoxane, an analogue of EDTA with intrinsic antineoplastic activity as well as strong iron binding properties, as both a prospective cardioprotective therapy for patients receiving anthracyclines and as an effective treatment for anthracycline extravasations. In this review, the molecular mechanisms by which the anthracyclines generate reactive oxygen species and interact with intracellular iron are examined to understand the cardioprotective mechanism of action of dexrazoxane and its ability to protect the subcutaneous tissues from anthracycline-induced tissue necrosis.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Animals
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Anthracyclines / administration & dosage
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Anthracyclines / adverse effects*
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Antibiotics, Antineoplastic / administration & dosage
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Antibiotics, Antineoplastic / adverse effects*
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Cardiotonic Agents / administration & dosage
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Cardiotonic Agents / adverse effects
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Cardiotonic Agents / therapeutic use*
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Extravasation of Diagnostic and Therapeutic Materials / complications
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Extravasation of Diagnostic and Therapeutic Materials / drug therapy*
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Extravasation of Diagnostic and Therapeutic Materials / metabolism
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Heart Diseases / chemically induced
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Heart Diseases / metabolism
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Heart Diseases / prevention & control*
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Humans
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Injections, Intravenous
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Iron / metabolism
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Razoxane / administration & dosage
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Razoxane / adverse effects
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Razoxane / therapeutic use*
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Reactive Oxygen Species / metabolism
Substances
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Anthracyclines
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Antibiotics, Antineoplastic
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Cardiotonic Agents
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Reactive Oxygen Species
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Razoxane
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Iron