Rybak Leonard P
Division of Otolaryngology, Department of Surgery, Southern Illinois University, School of Medicine, Springfield, Illinois 62794-9653, USA.
Curr Opin Otolaryngol Head Neck Surg. 2007 Oct;15(5):364-9. doi: 10.1097/MOO.0b013e3282eee452.
This review presents exciting new data published in the past year that help to elucidate the mechanisms of cisplatin ototoxicity. Recent research findings on otoprotection could lead to the development of novel protective agents. Cisplatin ototoxicity is a frequent and serious problem in patients. Strategies to ameliorate ototoxicity without interfering with the desired therapeutic effects are urgently needed.
Cisplatin ototoxicity appears to involve the production of reactive oxygen species in target tissues in the inner ear by activating an enzyme unique to the cochlea. This leads to a cascade resulting in oxidation of lipids and cell death. The upregulation of endogenous protective mechanisms in the cochlea or treatment with exogenous compounds reduces ototoxicity in cisplatin-treated animals. The only clinical trials reported to date with the putative protective agent, amifostine, have been disappointing.
The data summarized in this paper could lead to important clinical trials to determine whether the findings in experimental animals can translate into effective treatments to prevent cisplatin ototoxicity.
本综述介绍了过去一年发表的令人振奋的新数据，这些数据有助于阐明顺铂耳毒性的机制。近期关于耳保护的研究发现可能会推动新型保护剂的开发。顺铂耳毒性在患者中是一个常见且严重的问题。迫切需要在不干扰预期治疗效果的情况下改善耳毒性的策略。
顺铂耳毒性似乎涉及通过激活耳蜗特有的一种酶在内耳靶组织中产生活性氧。这会引发一系列反应，导致脂质氧化和细胞死亡。耳蜗内源性保护机制的上调或用外源性化合物治疗可降低顺铂处理动物的耳毒性。迄今为止报道的关于假定保护剂氨磷汀的唯一临床试验结果令人失望。
本文总结的数据可能会引发重要的临床试验，以确定实验动物中的发现能否转化为预防顺铂耳毒性的有效治疗方法。
