Rapamycin alleviates cisplatin-induced ototoxicity in vivo
Rapamycin alleviates cisplatin-induced ototoxicity in vivo
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DOI：
10.1016/j.bbrc.2014.04.123
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发表时间：
2014-06-13
影响因子：
3.1
通讯作者：
Xiao, Hongjun
中科院分区：
文献类型：
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作者：
Fang, Bin;Xiao, Hongjun
背景：顺铂引起的耳毒性影响全球高比例的新癌症患者。顺铂所致耳毒性的详细机制尚不完全清楚。方法：48只雄性Wistar大鼠随机分为6组，每组10只。三组大鼠均按16 mg/kg剂量腹腔注射顺铂，然后立即注射二甲基亚砜(DMSO)、雷帕霉素或氯喹(CQ)。其余三组分别给予雷帕霉素、CQ或生理盐水治疗。用听性脑干反应(ABR)检测大鼠的听力状况。分离血清测定氧化标记物丙二醛(MDA)水平，制作基底膜计数外毛细胞损失率，提取耳蜗软组织标本裂解分析微管相关蛋白轻链3(LC3)和Beclin-1的表达。结果：雷帕霉素治疗可明显减轻顺铂诱导的听力损失，减轻氧化应激，减轻与LC3-II/GAPDH比值上调和Beclin-1表达增加有关的毛细胞损伤。结论：雷帕霉素具有耳保护作用，其机制可能与减轻氧化损伤和诱导自噬有关。(C)2014 Elsevier Inc.保留所有权利。
Background: Cisplatin-induced ototoxicity affects a high percentage of new cancer patients worldwide. The detailed mechanism of cisplatin-induced ototoxicity is not completely understood. We investigated whether rapamycin could protect rats from cisplatin-induced ototoxicity.Methods: Forty-eight male Wistar rats were randomly divided into six groups. Three groups were intraperitoneally (IP) infused with cisplatin at a dose of 16 mg/kg and immediately injected with either dimethylsulfoxide (DMSO), rapamycin, or chloroquine (CQ). The remaining three groups were treated with rapamycin, CQ or saline alone. The auditory brainstem response (ABR) test was performed to detect the rats' hearing status. Serum was isolated to measure the level of the oxidative marker malondialdehyde (MDA), the basilar membrane was prepared to count the outer hair cell loss, and soft tissue samples extracted from the cochleae were lysed to analyze the microtubule-associated protein light chain 3 (LC3) and Beclin-1.Results: The rapamycin treatment significantly attenuated cisplatin-induced hearing loss, decreased oxidative stress, and alleviated the hair cell damage that was associated with the upregulation of the LC3-II/GAPDH ratio and increased Beclin-1 expression.Conclusion: Our results demonstrated that rapamycin has an otoprotective effect; it attenuates cisplatin-induced ototoxicity, probably by attenuating oxidative damage and inducing autophagy. (c) 2014 Elsevier Inc. All rights reserved.