Mills C D, Loos B M, Henley C M
The Bobby R. Alford Department of Otorhinolaryngology and Communicative Sciences, Baylor College of Medicine, Houston, TX 77030, USA.
Hear Res. 1999 Feb;128(1-2):75-9. doi: 10.1016/s0378-5955(98)00190-7.
Although clinical observations suggest that males are more susceptible than females to ototoxic drugs, controlled experimental studies investigating gender susceptibility have not been performed. Aminoglycosides initially attack the cochlea's outer hair cells (OHCs). We investigated the effects of the aminoglycoside, kanamycin, on electrophysiological function of OHCs in male and female rats. Animals were grouped by gender and treated with kanamycin (400 mg/kg/day kanamycin base, intramuscular injection) or equivolume normal saline. Administration was continued until distortion product otoacoustic emissions (DPOAEs) suggested a loss in OHC function in kanamycin-treated rats. Males treated with kanamycin showed changes in DPOAE thresholds and amplitudes as early as treatment day 10 which spread to all test frequencies by treatment day 13. In contrast, females treated with kanamycin did not show significant changes in thresholds or amplitudes until treatment day 22. The mechanism of increased male susceptibility to kanamycin cochleotoxicity has not been determined.
尽管临床观察表明，男性比女性更容易受到耳毒性药物的影响，但尚未进行过调查性别易感性的对照实验研究。氨基糖苷类药物最初会攻击耳蜗的外毛细胞（OHC）。我们研究了氨基糖苷类药物卡那霉素对雄性和雌性大鼠OHC电生理功能的影响。动物按性别分组，并用卡那霉素（400mg/kg/天卡那霉素碱，肌肉注射）或等体积生理盐水治疗。持续给药直至畸变产物耳声发射（DPOAE）表明卡那霉素治疗的大鼠OHC功能丧失。用卡那霉素治疗的雄性大鼠早在治疗第10天就出现了DPOAE阈值和振幅的变化，到治疗第13天，这些变化扩展到所有测试频率。相比之下，用卡那霉素治疗的雌性大鼠直到治疗第22天才出现阈值或振幅的显著变化。男性对卡那霉素耳蜗毒性易感性增加的机制尚未确定。
