Department of Otolaryngology, Cumhuriyet University School of Medicine, Sivas, Turkey.
Department of Internal Medicine, Cumhuriyet University School of Medicine, Sivas, Turkey.
J Int Adv Otol. 2020 Apr;16(1):77-86. doi: 10.5152/iao.2019.5908.
Nilotinib has very few side effects, including neutropenia, thrombocytopenia, cardiotoxicity, high pancreatic lipase, ischemia, and vascular occlusion. We aimed to investigate whether short-term administration of nilotinib had ototoxic effects in rats.
Wistar-albino rats were categorized into three groups: group C (administered 0.25 mL of distilled water, no nilotinib), group N-20 (administered 20 mg/kg/day of nilotinib dissolved in distilled water), and group N-50 (administered 50 mg/kg/day of nilotinib dissolved in distilled water). A single dose was administered once per day, at the same hour, over 21 days. Auditory brainstem response (ABR) thresholds were recorded on day 0 and day 21.
There were no changes in ABR threshold values obtained on day 0 (baseline) and on day 21 across all three groups. A statistically significant difference was not found in terms of the mean latency of waves V and III, interpeak latency values of waves III-V, and amplitude ratios of waves III-V and V/Va at baseline and on day 21 across all three groups on within-group or between-group evaluation.
Consequently, further studies are needed that involve different drug doses, prolonged administration of drugs, as well as distortion otoacoustic emission test for the evaluation of cochlear activation and ABR. Furthermore, histopathological studies are needed to indicate whether the cochlea is affected to prove that nilotinib has definitively no ototoxic effect.
尼洛替尼的副作用很少,包括中性粒细胞减少症、血小板减少症、心脏毒性、高胰腺脂肪酶、缺血和血管闭塞。我们旨在研究尼洛替尼短期给药是否会对大鼠产生耳毒性作用。
Wistar 白化大鼠分为三组:C 组(给予 0.25 mL 蒸馏水,无尼洛替尼)、N-20 组(给予 20 mg/kg/天溶于蒸馏水的尼洛替尼)和 N-50 组(给予 50 mg/kg/天溶于蒸馏水的尼洛替尼)。每天同一时间给予一次单次剂量,共 21 天。在第 0 天和第 21 天记录听觉脑干反应(ABR)阈值。
三组的 ABR 阈值在第 0 天(基线)和第 21 天都没有变化。在组内或组间评估中,三组在基线和第 21 天的波 V 和 III 的平均潜伏期、波 III-V 的峰间潜伏期值以及波 III-V 和 V/Va 的振幅比均无统计学意义差异。
因此,需要进行进一步的研究,包括不同的药物剂量、药物的延长给药以及畸变耳声发射测试,以评估耳蜗的激活和 ABR。此外,还需要进行组织病理学研究,以表明耳蜗是否受到影响,以证明尼洛替尼确实没有耳毒性作用。