Effect of 4-methylthiobenzoic acid on cisplatin-induced ototoxicity in the rat
Effect of 4-methylthiobenzoic acid on cisplatin-induced ototoxicity in the rat
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DOI：
10.1016/s0378-5955(99)00017-9
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发表时间：
1999-05-01
期刊：
影响因子：
2.8
通讯作者：
Rybak, LP
中科院分区：
文献类型：
--
作者：
Kamimura, T;Whitworth, CA;Rybak, LP
本研究的目的是调查的有效性4-甲硫基苯甲酸（MTBA）作为保护剂对顺铂（CDDP）诱导的Corti器官表面结构的变化，相比电生理变化。采用听性脑干反应（ABR）评价电生理变化，扫描电镜（SEM）评价形态学变化。雄性Wistar大鼠接受治疗前ABR的点击，并在2，4，8，16，和32 kHz的纯音。三组大鼠分别腹腔注射MTBA（250 mg/kg）、(2)CDDP（16 mg/kg，腹腔注射），(3)CDDP+MTBA。(16 mg/kg，腹腔注射+ 250 mg/kg，i.p.）。给药后3天进行治疗后ABR，处死大鼠。取耳蜗，用扫描电镜观察耳蜗Corti器表面，特别是耳蜗顶、中、底回的内毛细胞和外毛细胞的数量。在第一天和最后一天测量动物体重。ABR阈值变化和耳蜗高频区（基转）毛细胞损失之间有很好的相关性，而在较低的测试频率（中转）的阈值变化似乎是耳蜗更微妙的变化的结果。MTBA对顺铂诱导的ABR阈值变化在所有测试频率以及毛细胞损失提供了有效的保护。MTBA还可以防止体重减轻。(C)1999 Elsevier Science B. V.保留所有权利。
The purpose of this study was to investigate the effectiveness of 4-methylthiobenzoic acid (MTBA) as a protection agent against cisplatin (CDDP)-induced changes in organ of Corti surface structure, compared to electrophysiological changes. Electrophysiological change was assessed using auditory brainstem response (ABR) and morphological changes were assessed using scanning electron microscopy (SEM). Male Wistar rats underwent pre-treatment ABRs in response to clicks, and tone bursts at 2, 4, 8, 16, and 32 kHz. The three groups of rats were injected as follows: (1) MTBA (250 mg/kg, i.p.), (2) CDDP (16 mg/kg, i.p.), (3) CDDP+MTBA. (16 mg/kg, i.p.+250 mg/kg, i.p.). Post-treatment ABRs were performed 3 days after drug administration and rats were sacrificed. Their cochleae were harvested and SEM was used to examine the surface of the organ of Corti, specifically the number of inner hair cells (IHCs) and outer hair cells (OHCs) in the apical, middle and basal turns of the cochlea. Animal weight was measured on the first and final days. There was a good correlation between ABR threshold changes and hair cell loss in the high frequency region of the cochlea (basal turn), while threshold changes in the lower test frequencies (middle turn) appeared to be the result of more subtle changes in the cochlea. MTBA provided effective protection against cisplatin-induced ABR threshold changes at all test frequencies as well as hair cell loss. MTBA also protected against body weight loss. (C) 1999 Elsevier Science B.V. All rights reserved.