D-Methionine provides excellent protection from cisplatin ototoxicity in the rat
D-Methionine provides excellent protection from cisplatin ototoxicity in the rat
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DOI：
10.1016/s0378-5955(96)00152-9
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发表时间：
1996-12-01
期刊：
影响因子：
2.8
通讯作者：
Hughes, L
中科院分区：
文献类型：
--
作者：
Campbell, KCM;Rybak, LP;Hughes, L
顺铂（CDDP）是一种广泛使用的化疗药物。不幸的是，CDDP具有高度耳毒性。我们测试了D-蛋氨酸（D-Met），含硫化合物，作为耳保护剂在雄性Wistar大鼠。获得了五组动物的完整数据集，每组五只动物，包括给药对照组（16 mg/kg CDDP）、未给药对照组（给予等量生理盐水）和在16 mg/kg CDDP给药前30分钟接受75、150或300 mg/kg D-Met的三个组。在给药前和给药后3天，获得对短声和1 kHz、4 kHz、8 kHz和14 kHz短纯音刺激的听觉脑干反应（ABR）阈值。用扫描电镜观察耳蜗顶、中、底回的外毛细胞。在第一天和最后一天测量动物体重。即使在最低水平下，D-Met也提供了优异的耳保护，如通过ABR和SEM测量的，300 mg/kg剂量获得了完全的耳保护。D-Met还显著降低了体重减轻和死亡率。所有接受D-Met的动物（15/15）均存活至研究期结束，而接受治疗的对照组动物仅为5/10。
Cisplatin (CDDP) is a widely used chemotherapeutic agent. Unfortunately, CDDP is highly ototoxic. We tested D-methionine (D-Met), a sulfur containing compound, as an otoprotectant in male Wistar rats. Complete data sets were obtained for five groups of five animals each, including a treated control group (16 mg/kg CDDP), an untreated control group (administered an equivalent volume of saline) and three groups that received either 75, 150, or 300 mg/kg D-Met 30 min prior to the 16 mg/kg CDDP dosing. Auditory brainstem response (ABR) thresholds were obtained in response to clicks, and 1 kHz, 4 kHz, 8 kHz, and 14 kHz toneburst stimuli, before and 3 days after drug administration. Scanning electron microscopy (SEM) was used to examine the outer hair cells of the apical, middle and basal turns of the cochlea. Animal weight was measured on the first and final day. D-Met provided excellent otoprotection even at the lowest level with complete otoprotection obtained for the 300 mg/kg dosing as measured by both ABR and SEM. D-Met also markedly reduced weight loss and mortality. All animals receiving D-Met (15/15) survived to the end of the study period as opposed to only 5/10 of the treated controls.