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Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug?

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Abstract

Dexrazoxane is highly effective in reducing anthracycline-induced cardiotoxicity and extravasation injury and is used clinically for these indications. Dexrazoxane has two biological activities: it is a prodrug that is hydrolyzed to an iron chelating EDTA-type structure and it is also a strong inhibitor of topoisomerase II. Doxorubicin is able to be reductively activated to produce damaging reactive oxygen species. Iron-dependent cellular damage is thought to be responsible for its cardiotoxicity. The available experimental evidence supports the conclusion that dexrazoxane reduces doxorubicin cardiotoxicity by binding free iron and preventing site-specific oxidative stress on cardiac tissue. However, it cannot be ruled out that dexrazoxane may also be protective through its ability to inhibit topoisomerase II.

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Acknowledgments

This work was supported by the Canadian Institutes of Health Research, the Canada Research Chairs program and a Canada Research Chair in Drug Development for Brian Hasinoff.

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Authors and Affiliations

  1. Faculty of Pharmacy, University of Manitoba, 50 Sifton Road, Winnipeg, Manitoba, Canada, R3T 2N2

    Brian B. Hasinoff

  2. Division of Applied Pharmacology Research (HFD–910), Center for Drug Evaluation and Research Food and Drug Administration, Silver Spring, MA, 20993, USA

    Eugene H. Herman

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  1. Brian B. Hasinoff
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  2. Eugene H. Herman
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Correspondence to Brian B. Hasinoff.

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Hasinoff, B.B., Herman, E.H. Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug?. Cardiovasc Toxicol 7, 140–144 (2007). https://doi.org/10.1007/s12012-007-0023-3

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  • DOI: https://doi.org/10.1007/s12012-007-0023-3

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