顺铂诱导的肾毒性和耳毒性的综合观点。
An integrated view of cisplatin-induced nephrotoxicity and ototoxicity.
作者信息
Karasawa Takatoshi, Steyger Peter S
机构信息
Oregon Hearing Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States.
Oregon Hearing Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States.
出版信息
Toxicol Lett. 2015 Sep 17;237(3):219-27. doi: 10.1016/j.toxlet.2015.06.012. Epub 2015 Jun 20.
Abstract
Cisplatin is one of the most widely-used drugs to treat cancers. However, its nephrotoxic and ototoxic side-effects remain major clinical limitations. Recent studies have improved our understanding of the molecular mechanisms of cisplatin-induced nephrotoxicity and ototoxicity. While cisplatin binding to DNA is the major cytotoxic mechanism in proliferating (cancer) cells, nephrotoxicity and ototoxicity appear to result from toxic levels of reactive oxygen species and protein dysregulation within various cellular compartments. In this review, we discuss molecular mechanisms of cisplatin-induced nephrotoxicity and ototoxicity. We also discuss potential clinical strategies to prevent nephrotoxicity and ototoxicity and their current limitations.
摘要
顺铂是治疗癌症最广泛使用的药物之一。然而，其肾毒性和耳毒性副作用仍然是主要的临床限制。最近的研究增进了我们对顺铂诱导的肾毒性和耳毒性分子机制的理解。虽然顺铂与DNA结合是增殖（癌）细胞中的主要细胞毒性机制，但肾毒性和耳毒性似乎是由各种细胞区室内活性氧的毒性水平和蛋白质失调所致。在本综述中，我们讨论了顺铂诱导的肾毒性和耳毒性的分子机制。我们还讨论了预防肾毒性和耳毒性的潜在临床策略及其当前的局限性。
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