Campbell Kathleen C M, Meech Robert P, Klemens James J, Gerberi Michael T, Dyrstad Sara S W, Larsen Deb L, Mitchell Diana L, El-Azizi Mohammed, Verhulst Steven J, Hughes Larry F
Southern Illinois University, School of Medicine, Springfield, IL 62794-9629, USA.
Hear Res. 2007 Apr;226(1-2):92-103. doi: 10.1016/j.heares.2006.11.012. Epub 2007 Jan 16.
A number of otoprotective agents are currently being investigated. Various types of agents have been found in animal studies to protect against hearing loss induced by cisplatin, carboplatin, aminoglycosides, or noise exposure. For over a decade we have been investigating D-methionine (D-met) as an otoprotective agent. Studies in our laboratory and others around the world have documented D-met's otoprotective action, in a variety of species, against a variety of ototoxic insults including cisplatin-, carboplatin-, aminoglycoside- and noise-induced auditory threshold elevations and cochlear hair cell loss. For cisplatin-induced ototoxicity, protection of the stria vascularis has also been documented. Further D-met has an excellent safety profile. D-met may act as both a direct and indirect antioxidant. In this report, we provide the results of three experiments, expanding findings in D-met protection in three of our translational research areas: protection from platinum based chemotherapy-, aminoglycoside- and noise-induced hearing loss. These experiments demonstrate oral D-met protection against cisplatin-induced ototoxicity, D-met protection against amikacin-induced ototoxicity, and D-met rescue from permanent noise-induced hearing loss when D-met is initiated 1h after noise exposure. These studies demonstrate some of the animal experiments needed as steps to translate a protective agent from bench to bedside.
目前正在研究多种耳保护剂。在动物研究中已发现各类药剂可预防由顺铂、卡铂、氨基糖苷类药物或噪声暴露引起的听力损失。十多年来,我们一直在研究D-蛋氨酸(D-met)作为一种耳保护剂。我们实验室及全球其他实验室的研究已证明,在多种物种中,D-met对多种耳毒性损伤具有耳保护作用,这些损伤包括顺铂、卡铂、氨基糖苷类药物和噪声引起的听觉阈值升高及耳蜗毛细胞损失。对于顺铂诱导的耳毒性,也已证明其对血管纹具有保护作用。此外,D-met具有出色的安全性。D-met可能兼具直接和间接抗氧化剂的作用。在本报告中,我们提供了三个实验的结果,扩展了我们在三个转化研究领域中D-met保护作用的研究结果:预防铂类化疗、氨基糖苷类药物和噪声引起的听力损失。这些实验证明了口服D-met对顺铂诱导的耳毒性具有保护作用,D-met对阿米卡星诱导的耳毒性具有保护作用,以及在噪声暴露1小时后开始使用D-met可使永久性噪声引起的听力损失得到挽救。这些研究展示了将一种保护剂从实验室应用到临床所需的一些动物实验步骤。