Protection against cisplatin-induced ototoxicity by N-acetylcysteine in a rat model
Protection against cisplatin-induced ototoxicity by N-acetylcysteine in a rat model
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DOI：
10.1016/j.heares.2004.02.007
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发表时间：
2004-07-01
期刊：
影响因子：
2.8
通讯作者：
Neuwelt, EA
中科院分区：
文献类型：
--
作者：
Dickey, DT;Muldoon, LL;Neuwelt, EA
顺铂 (CDDP) 是一种广泛使用的化疗药物，具有高度耳毒性。动物研究和临床试验表明，硫代硫酸盐可以预防铂引起的耳毒性。本研究研究了大鼠 CDDP 耳毒性的新模型，并测试了在给予 CDDP 之前给予 N-乙酰半胱氨酸 (NAC) 的潜在化学保护作用。 Long Evans 大鼠在静脉内 (IV) 输注生理盐水 (n = 8) 或 NAC 400 mg/kg (n = 8) 15 分钟后，通过逆行右外颈动脉输注将 CDDP 6 mg/kg 递送至主动脉，从而灌注椎动脉。随后的组在 CDDP 前 30 分钟 (n = 7) 和 CDDP 后 4 小时 (n = 7) 接受 NAC 类似治疗。治疗后 7 天，在 4-20 kHz 下测试听觉脑干反应 (ABR) 阈值，并与基线 ABR 值进行比较。 NAC 治疗的大鼠在所有时间间隔内均未表现出与基线值相比的显着变化，而盐水治疗的大鼠则表现出明显的耳毒性，尤其是在较高频率下。此外，在 CDDP 前 15 分钟用 NAC 治疗的大鼠表现出较低的 CDDP 总体毒性，治疗后 7 天的体重减轻证明了这一点（盐水平均值 = -39.63 g；NAC 平均值 = -21.13 g；p = 0.0084）。这些数据表明，NAC 治疗可以预防 CDDP 诱导的大鼠耳毒性。 (C) 2004 Elsevier B.V. 保留所有权利。
Cisplatin (CDDP) is a widely used chemotherapeutic agent that is highly ototoxic. Animal studies and clinical trials have shown that thiosulfates can protect against platinum-induced ototoxicity. This study investigated a new model for CDDP ototoxicity in the rat, and tested the potential chemoprotective effect of administering N-acetylcysteine (NAC) before giving CDDP. Long Evans rats were treated with CDDP 6 mg/kg delivered to the aorta via a retrograde right external carotid artery infusion, 15 min after intravenous (IV) infusion of saline (n = 8) or NAC 400 mg/kg (n = 8), such that the vertebral arteries were perfused. Subsequent groups were similarly treated with NAC 30 min before (n = 7) and 4 h after (n = 7) CDDP. Auditory brainstem response (ABR) thresholds were tested at 4-20 kHz, 7 days after treatment and compared to baseline ABR values. The NAC-treated rats exhibited no significant change from baseline values at all time intervals, while the saline-treated rats showed marked ototoxicity, especially at higher frequencies. Furthermore, the rats treated with NAC 15 min before CDDP exhibited less overall toxicity to CDDP, as evidenced in weight loss 7 days post-treatment (mean for saline = -39.63 g; mean for NAC = -21.13 g; p = 0.0084). These data show that treatment with NAC can prevent CDDP-induced ototoxicity in rats. (C) 2004 Elsevier B.V. All rights reserved.