Electrophysiological findings in the Sprague-Dawley rat induced by moderate-dose carboplatin
Electrophysiological findings in the Sprague-Dawley rat induced by moderate-dose carboplatin
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DOI：
10.1016/s0378-5955(03)00141-2
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发表时间：
2003-08-01
期刊：
影响因子：
2.8
通讯作者：
Martini, A
中科院分区：
文献类型：
--
作者：
Hatzopoulos, S;Petruccelli, J;Martini, A
卡铂是第二代含铂抗肿瘤药物，可选择性改变龙猫柯蒂氏器内毛细胞（IHC）的微机械功能。来自最近研究的数据 [Wake 等人，Acta Otolaryngol。 116 (1996) 374-381]，使用龙猫模型，表明中等剂量的卡铂改变 OHC 的传出反馈环路增益。本研究旨在利用畸变产物耳声发射（DPOAE）评估 Sprague-Dawley 大鼠中可能的“传出反馈改变机制”。通过 30 分钟腹腔注射施用中等剂量的卡铂（50 mg/kg 体重）。输液。从一组 12 只大鼠中获取治疗前和 72 小时后的 DPOAE 和听觉脑干反应 (ABR) 记录。动物用氯胺酮-阿托品麻醉进行麻醉，分两个阶段进行。使用四种不对称协议记录 DPOAE 响应（三次失真产物）：P1 = 60-50、P2 = 50-40、P3 = 40-30 和 P4 = 30-20 dB SPL（声压级），频率范围为 4.0 至 16 kHz。使用 100 至 30 dB SPL 范围内的刺激，获得频率 8.0、10.0、20.0 和 30 kHz 的双极喀哒声和音尖的 ABR 响应。在 30 kHz 处观察到 15 dB 的显着 ABR 阈值偏移，在 20、16 和 10 kHz 处观察到 10 dB 的偏移。治疗前和治疗后 DPOAE 反应的比较没有揭示方案 P1、P2 和 P4 的任何显着变化。 P3 协议的数据表明 DPOAE 幅度降低。大鼠模型的研究结果表明，(a) 中等剂量的卡铂不会影响传出反馈环路 OHC 功能，(b) 不同物种的耳蜗对卡铂的敏感性不同，即使在中等剂量的情况下也是如此。 (C) 2003 Elsevier B.V. 保留所有权利。
Carboplatin is a second generation platinum-containing anti-tumor drug which selectively alters the micromechanical function of the inner hair cells (IHCs) of the organ of Corti in the chinchilla. Data from a recent study [Wake et al., Acta Otolaryngol. 116 (1996) 374-381], using the chinchilla model, have suggested that a moderate dose of carboplatin alters the efferent feedback loop gain of the OHCs. The present study was designed to evaluate the possible 'efferent feedback alteration mechanism' in the Sprague-Dawley rat using distortion product otoacoustic emissions (DPOAEs). A moderate dose of carboplatin (50 mg/kg body weight) was administered by a 30 min i.p. infusion. Pre- and 72-h post-treatment DPOAE and auditory brainstem response (ABR) recordings were acquired from a group of 12 rats. The animals were anesthetized with a ketamine-atropin anesthesia administered in two consecutive phases. The DPOAE responses (cubic distortion products) were recorded with four asymmetrical protocols: P1 = 60-50, P2 = 50-40, P3 = 40-30 and P4 = 30-20 dB SPL (sound pressure level), in the frequency range from 4.0 to 16 kHz. ABR responses were obtained for bipolar clicks and tone pips at the frequencies 8.0, 10.0, 20.0 and 30 kHz using stimuli in the range from 100 to 30 dB SPL. Significant ABR threshold shifts of 15 dB were observed at 30 kHz, and shifts of 10 dB at 20, 16 and 10 kHz. The comparison of pre- and post-treatment DPOAE responses did not reveal any significant changes for protocols P1, P2 and P4. Data from the P3 protocol indicated a decrease of the DPOAE amplitude. The findings from the rat model suggest that (a) moderate doses of carboplatin do not affect the efferent feedback loop OHC function and (b) the cochlear susceptibility to carboplatin across species is different, even at moderate-dose regimes. (C) 2003 Elsevier B.V. All rights reserved.