Kecioren Training and Research Hospital, Department of Otolaryngology, Ankara, Turkey.
Kecioren Training and Research Hospital, Department of Otolaryngology, Ankara, Turkey; Guven Private Hospital, Department of Audiology, Ankara, Turkey.
Braz J Otorhinolaryngol. 2022 Sep-Oct;88(5):651-656. doi: 10.1016/j.bjorl.2020.09.002. Epub 2020 Oct 4.
Aminoglycosides are widely known for their ototoxic side effects. Nevertheless, they are potent antibiotics used in the treatment of life-threatening conditions because of the current concern for antibiotic resistance. We hypothesized that creatine supplements which are believed to improve mitochondrial antioxidant defense system and maintain optimal energy homeostasis may improve the ototoxic side effects.
This study aimed to investigate the protective effects of creatine monohydrate against ototoxicity induced by amikacin in rats in an experimental animal model, using distortion product otoacoustic emissions and auditory brainstem response.
Twenty healthy rats were assigned to four groups (5 rats in each): the control group, the creatine monohydrate group, the amikacin group and the amikacin+creatine monohydrate group. The creatine monohydrate group received creatine at a dose of 2g/kg once daily via gastric gavage for 21 days. The amikacin group received amikacin at a dose of 600mg/kg by intramuscular injections once daily for 21 days. The amikacin+creatine monohydrate group received intramuscular injections of amikacin (600mg/kg) once daily for 21 days and creatine monohydrate (2g/kg) once daily via gastric gavage for 21 days. The control group received nothing. The distortion product otoacoustic emissions and auditory brainstem response measurements were performed on all rats on days 0, 7, 21.
Regarding auditory brainstem response values, a significant increase in the auditory threshold was observed in the amikacin group on day 21 (p< 0.001). The amikacin+creatine monohydrate group showed significantly lower levels of auditory brainstem response auditory thresholds on day 21 in comparison to the amikacin group (p< 0.001). Additionally, the control group and the amikacin+creatine monohydrate group did not differ significantly with respect to auditory brainstem response thresholds on treatment day 21 (p> 0.05). When we compare distortion product otoacoustic emissions values, there was no significant difference between the amikacin and amikacin+creatine monohydrate groups on day 7 (p> 0.05), However significantly greater distortion product otoacoustic emissions values were observed in the amikacin+creatine monohydrate group on day 21 compared to the amikacin group (p< 0.001).
Our findings demonstrate that creatine treatment protects against amikacin ototoxicity when given at a sufficient dose and for an adequate time period.
氨基糖苷类抗生素以其耳毒性副作用而闻名。然而,由于目前对抗生素耐药性的担忧,它们是治疗危及生命的疾病的有效抗生素。我们假设肌酸补充剂可以改善线粒体抗氧化防御系统并维持最佳能量稳态,可能会改善耳毒性副作用。
本研究旨在通过畸变产物耳声发射和听性脑干反应,在实验动物模型中研究肌酸单水合物对阿米卡星诱导的耳毒性的保护作用。
将 20 只健康大鼠分为四组(每组 5 只):对照组、肌酸单水合物组、阿米卡星组和阿米卡星+肌酸单水合物组。肌酸单水合物组通过胃灌胃给予肌酸单水合物 2g/kg,每日一次,连续 21 天。阿米卡星组通过肌肉注射给予阿米卡星 600mg/kg,每日一次,连续 21 天。阿米卡星+肌酸单水合物组连续 21 天每日通过胃灌胃给予肌酸单水合物 2g/kg,每日通过肌肉注射给予阿米卡星 600mg/kg。对照组什么也不接受。所有大鼠在第 0、7、21 天进行畸变产物耳声发射和听性脑干反应测量。
关于听性脑干反应值,在第 21 天,阿米卡星组的听觉阈值显著升高(p<0.001)。与阿米卡星组相比,阿米卡星+肌酸单水合物组在第 21 天的听性脑干反应听觉阈值显著降低(p<0.001)。此外,在治疗第 21 天,对照组和阿米卡星+肌酸单水合物组的听性脑干反应阈值无显著差异(p>0.05)。当我们比较畸变产物耳声发射值时,在第 7 天,阿米卡星组和阿米卡星+肌酸单水合物组之间没有显著差异(p>0.05)。然而,在第 21 天,阿米卡星+肌酸单水合物组的畸变产物耳声发射值显著高于阿米卡星组(p<0.001)。
我们的研究结果表明,在给予足够剂量和足够时间的肌酸治疗时,肌酸治疗可预防阿米卡星耳毒性。