Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug?
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.
Hasinoff
Brian B
BB
Faculty of Pharmacy, University of Manitoba, 50 Sifton Road, Winnipeg, Manitoba, Canada. B_Hasinoff@UManitoba.ca
Herman
Eugene H
EH
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002317:Cardiovascular Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004317:Doxorubicin / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006331:Heart Diseases / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011929:Razoxane / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D011355:Prodrugs; D059005:Topoisomerase II Inhibitors; D011929:Razoxane; D004317:Doxorubicin