MECHANISM OF CISPLATIN OTOTOXICITY - ANTIOXIDANT SYSTEM
MECHANISM OF CISPLATIN OTOTOXICITY - ANTIOXIDANT SYSTEM
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DOI：
10.1111/j.1600-0773.1995.tb00167.x
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发表时间：
1995-06-01
期刊：
影响因子：
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通讯作者：
RYBAK, LP
中科院分区：
文献类型：
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作者：
RAVI, R;SOMANI, SM;RYBAK, LP
顺铂的剂量和持续时间限制毒性作用是耳毒性和肾毒性。虽然有几项研究试图阐明肾毒性的原因，但对顺铂诱导耳毒性的原因知之甚少。因此，进行本研究以描述顺铂耳毒性的潜在机制。研究了急性剂量顺铂后，谷胱甘肽（GSH）、氧化型谷胱甘肽（GSSG）和丙二醛水平以及抗氧化酶活性[超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶]在耳蜗毒性中的作用。用不同剂量的顺铂处理雄性Wistar大鼠。治疗前进行听觉脑干诱发电位（ABR）检查，治疗后3天进行ABR和耳蜗内电位检查。急性耳蜗毒性（耳毒性）表现为ABR对各种刺激（2、8、16和32 kHz的短声和短纯音）的听阈升高和I波潜伏期延长。与对照动物相比，顺铂治疗大鼠的耳蜗内电位降低（50%对照）。将大鼠处死并分离耳蜗。测定GSH、GSSG、丙二醛含量及抗氧化酶活性。顺铂耳毒性与顺铂给药后耳蜗GSH降低[0.45+/-0.012 nmol/mg]相关，而对照耳蜗GSH为0.95+/-012 nmol/mg（P
The dose and duration limiting toxic effects of cisplatin are ototoxicity and nephrotoxicity. While several studies have attempted to shed some light on the causes of nephrotoxicity, the reasons for ototoxicity induced by cisplatin are poorly understood. Therefore, this investigation was undertaken to delineate the potential mechanisms underlying cisplatin ototoxicity. The role of glutathione (GSH), oxidized glutathione (GSSG) and malondialdehyde levels, and antioxidant enzyme activities [superoxide dismutase, catalase, GSH peroxidase, and GSH reductase] were examined in cochlear toxicity following an acute dose of cisplatin. Male Wistar rats were treated with various doses of cisplatin. Pretreatment auditory brain stem evoked responses (ABR) were performed and then post-treatment ABRs and endocochlear potentials were also performed after three days. Acute cochlear toxicity (ototoxicity) was evidenced as elevated hearing thresholds and prolonged wave I latencies in response to various stimuli (clicks and tone bursts at 2, 8, 16 and 32 kHz) on ABRs. The endocochlear potentials were reduced (50% control) in cisplatin-treated rats as compared to control animals. The rats were sacrified and cochleae isolated. The GSH, GSSG and malondialdehyde levels, and antioxidant enzyme activities were determined. Cisplatin ototoxicity correlated with a decrease in cochlear GSH [0.45+/-0.012 nmol/mg] after cisplatin administration compared to 0.95+/-012 nmol/mg in control cochleae (P