Ferreira A L A, Matsubara L S, Matsubara B B
Department of Internal Medicine, Botucatu Medical School, UNESP- São Paulo State University, Botucatu, SP, Brasil.
Cardiovasc Hematol Agents Med Chem. 2008 Oct;6(4):278-81. doi: 10.2174/187152508785909474.
The anthracyclines constitute a group of drugs widely used for the treatment of a variety of human tumors. However, the development of irreversible cardiotoxicity has limited their use. Anthracycline-induced cardiotoxicity can persist for years with no clinical symptoms. However, its prognosis becomes poor after the development of overt heart failure, possibly even worse than ischemic or idiopathic dilated cardiomyopathies. Due to the successful action of anthracyclines as chemotherapic agents, several strategies have been tried to prevent/attenuate their side effects. Although anthracycline-induced injury appears to be multifactorial, a common denominator among most of the proposed mechanisms is cellular damage mediated by reactive oxygen species. However, it remains controversial as to whether antioxidants can prevent such side effects given that different mechanisms may be involved in acute versus chronic toxicity. The present review applies a multisided approach to the critical evaluation of various hypotheses proposed over the last decade on the role of oxidative stress in cardiotoxicity induced by doxorubicin, the most used anthracycline agent. The clinical diagnosis and treatment is also discussed.
蒽环类药物是一类广泛用于治疗多种人类肿瘤的药物。然而，不可逆心脏毒性的出现限制了它们的应用。蒽环类药物诱导的心脏毒性可在无临床症状的情况下持续数年。然而，在出现明显心力衰竭后，其预后变差，甚至可能比缺血性或特发性扩张型心肌病更差。由于蒽环类药物作为化疗药物的成功作用，人们尝试了多种策略来预防/减轻其副作用。尽管蒽环类药物诱导的损伤似乎是多因素的，但大多数提出的机制中的一个共同因素是活性氧介导的细胞损伤。然而，鉴于急性毒性和慢性毒性可能涉及不同机制，抗氧化剂是否能预防此类副作用仍存在争议。本综述采用多方面的方法对过去十年中提出的关于氧化应激在最常用的蒽环类药物阿霉素诱导的心脏毒性中的作用的各种假说进行批判性评估。还讨论了临床诊断和治疗。
