Investigation of ototoxic effects of taxol on a mice model
Investigation of ototoxic effects of taxol on a mice model
复制标题
DOI：
10.1016/j.ijporl.2005.11.011
复制
发表时间：
2006-05-01
影响因子：
1.5
通讯作者：
Akyol, M
中科院分区：
文献类型：
--
作者：
Ahmet, A;Orhan, A;Akyol, M
目的：探讨紫杉醇对小鼠内耳的作用。方法：对56只白化病瑞士小鼠的112只耳进行了这项研究。所有动物均接受双侧基线听觉脑干反应（ABR）测试，并获得基线峰值等效声压级（PESPL）。将小鼠随机分配到七个组，包括一个对照组和六个研究组。对照组不接受药物，而第1-6组中的小鼠腹膜内接受1 x 60、1 x 20、2 x 20、3 x 20、4 x 20和5 x 20 mg/kg紫杉醇。在末次给药后3周进行对照ABR评估。然后在麻醉状态下处死动物，并从其颞骨上解剖大疱（包括耳蜗）。苏木精-伊红和Masson的三色染色被用来显示结缔组织，和高碘酸希夫（PAS）染色被用来突出上皮元素。结果：在所有的组中观察到的听力水平显着下降，收到紫杉醇。未观察到剂量与听力损失程度之间的相关性。对照组的切片显示无组织病理学异常（白色），研究组的切片显示螺旋利姆布斯和血管纹的上皮细胞空泡化，成纤维细胞空泡化，螺旋利姆布斯中成纤维细胞的数量减少。在组织学上，耳蜗发生退行性变化，类似于水杨酸盐和干扰素α 2a耳毒性中发生的退行性变化，这些变化被认为是可逆的。没有感觉细胞损失。听力下降开始于小于或等于20 mg/kg的剂量，并且在该剂量后不具有剂量依赖性。强烈建议在人类受试者使用本品之前和期间进行听力监测和听力学评价。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Objective: To investigate the effects of taxol on the inner ear in a mice model. Methods: This study was performed on 112 ears of 56 albino Swiss mice. All animals underwent baseline auditory brainstem response (ABR) testing bilaterally and baseline Peak Equivalent Sound Pressure Levels (PESPLs) were obtained. The mice were randomly assigned to seven groups consisting of one control and six study groups. The control group received no medications while the mice in groups 1-6 received 1 x 60, 1 x 20, 2 x 20, 3 x 20, 4 x 20 and 5 x 20 mg/kg taxot intraperitoneatly. Control ABR assessments were performed 3 weeks after the last dose. The animals were then sacrificed while still anaesthetised and the bullae (cochleae included) were dissected from their temporal bones. Haematoxylin-eosin and Masson's trichrome stains were used to demonstrate connective tissue, and periodic acid Schiff (PAS) stain was used to highlight epithelial elements.Results: Significant decreases in the hearing levels were observed in all the groups which received taxot. No correlation was observed between the dose given and the degree of hearing loss. The sections from the control group showed no histopathologic abnormalities white the sections from the study groups demonstrated vacuolisation in the epithelial cells of the spiral limbus, and the stria vascularis, vacuolisation of the fibroblasts and decreasing the number of the fibroblasts in the spiral limbus.Conclusion: Taxol causes mild to moderate sensorineural hearing loss in mice. Histopathologically, there were degenerative changes in the cochlea resembling the ones that take place in salisytate and interferon alpha 2a ototoxicity which are thought to be reversible. There was no sensory cell loss. The hearing toss begins with doses less than or equal to 20 mg/kg and is not dose dependent after this dose. Hearing monitorisation with audiologic evaluation is strongly recommended before and during the use of the drug in human subjects. (c) 2005 Elsevier Ireland Ltd. All rights reserved.