University of Manitoba, and Sylvie Berard: Health Sciences Centre, Winnipeg, MB.
J Otolaryngol Head Neck Surg. 2011 Feb;40 Suppl 1:S45-8.
Hearing loss owing to ototoxicity in humans is usually presumed to be irreversible and stable. Most articles in the literature study the effects of ototoxic agents such as cisplatin only over a few days or weeks. This study focused on the recovery of hearing over several months in mice. The same treatment was applied to guinea pigs to determine whether there were significant differences in response between the two species.
Thirty-two mice and 37 guinea pigs were randomized to receive either saline or cisplatin (15 mg/kg). After this exposure, we performed auditory brainstem response (ABR) testing on the mice over 8 months and on the guinea pigs for 1 month.
Hearing loss owing to cisplatin shows significant variability between and within species. In mice, hearing loss is maximal at about 17 dB during the third month after cisplatin administration but actually improves to the level attributable to presbyacusis. Guinea pigs, however, experience greater, approximately 25 dB hearing loss within a month of administration of the same dose of cisplatin, tested with the same protocol.
In general, ototoxicity end points should be assessed more than 1 month after exposure for animals. Our observation that hearing loss is incomplete before 1 month in mice opens the possibility of studies for preventive treatment during that time.
由于耳毒性导致的人类听力损失通常被认为是不可逆转和稳定的。文献中的大多数文章仅研究顺铂等耳毒性药物在数天或数周内的影响。本研究重点关注小鼠数月内听力的恢复情况。对豚鼠进行了相同的治疗，以确定两种物种之间的反应是否存在显著差异。
32 只小鼠和 37 只豚鼠随机分为盐水或顺铂（15mg/kg）组。暴露后，我们对小鼠进行了 8 个月的听觉脑干反应（ABR）测试，对豚鼠进行了 1 个月的测试。
顺铂引起的听力损失在物种之间和物种内具有显著的可变性。在小鼠中，顺铂给药后第三个月的听力损失最大约为 17dB，但实际上会改善到与衰老相关的听力损失水平。然而，豚鼠在接受相同剂量顺铂治疗后一个月内的听力损失更大，约为 25dB，使用相同的方案进行测试。
一般来说，动物的耳毒性终点应在暴露后 1 个月以上进行评估。我们观察到，在小鼠中，听力损失在 1 个月前尚未完全恢复，这为在此期间进行预防治疗的研究提供了可能性。
