Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug?
Dexrazoxane: how it works in cardiac and tumor cells. Is it a prodrug or is it a drug?
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DOI：
10.1007/s12012-007-0023-3
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发表时间：
2007-01-01
影响因子：
3.2
通讯作者：
Herman, Eugene H.
中科院分区：
文献类型：
--
作者：
Hasinoff, Brian B.;Herman, Eugene H.
Dexrazoxane在减少蒽环类药物引起的心脏毒性和外渗损伤方面非常有效，临床上用于这些适应症。Dexrazoxane具有两种生物活性：它是一种前药，被水解成铁螯合edta型结构，也是一种强的拓扑异构酶II抑制剂。阿霉素能够被还原激活以产生有害的活性氧。铁依赖性细胞损伤被认为是其心脏毒性的原因。现有的实验证据支持dexrazoxane通过结合游离铁和防止心脏组织部位特异性氧化应激来降低阿霉素心脏毒性的结论。然而，不能排除右razoxane也可能通过其抑制拓扑异构酶II的能力起到保护作用。
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.