Mansour Yusra, Haddad LeAnn, Breeden Zachary, Kulesza Randy J
Department of Otolaryngology - Head and Neck Surgery, Henry Ford Macomb Hospital, Clinton Township, MI, USA.
Department of Anatomy, Lake Erie College of Osteopathic Medicine, 1858 West Grandview Blvd Erie, Erie, PA, 16504, USA.
Exp Brain Res. 2024 Dec 10;243(1):20. doi: 10.1007/s00221-024-06967-9.
Gentamicin is a bactericidal aminoglycoside antibiotic that broadly targets Gram-negative microbes. Both human and animal studies have shown that administration of gentamicin is ototoxic by several routes of administration and results in sensorineural hearing loss due to damaged hair cell at the base of the cochlea. However, gentamicin is also administered intranasally to treat sinusitis in humans, but no animal studies have examined ototoxicity of gentamicin administered via this route. We hypothesized that intranasal irrigation of gentamicin will result in ototoxicity and impaired auditory function similar to systemic delivery. We investigated this hypothesis in Sprague-Dawley rats that received intranasal irrigations of gentamicin or saline from postnatal day (P) 21-31. We examined auditory function by assessing brainstem auditory evoked potentials in response to both broadband clicks and pure tone-pips (4, 8, 16, 24 and 32 kHz) on P41. We found significant changes in auditory function in gentamicin-exposed animals. Specifically, gentamicin-exposed animals had significantly higher thresholds in response to both clicks and tone-pips. In response to broadband clicks, there were no changes in latency for waves I through IV. However, we found significantly longer wave and interwave latencies for all waves in response to the 24 kHz tone-pip. Together, these findings suggest that intranasal administration of gentamicin results in impaired auditory function consistent with other routes of delivery.
庆大霉素是一种杀菌性氨基糖苷类抗生素，广泛作用于革兰氏阴性微生物。人体和动物研究均表明，通过多种给药途径使用庆大霉素具有耳毒性，会因耳蜗底部毛细胞受损导致感音神经性听力损失。然而，庆大霉素也可经鼻内给药用于治疗人类鼻窦炎，但尚无动物研究考察过通过该途径给药的庆大霉素的耳毒性。我们推测，经鼻内冲洗庆大霉素会导致耳毒性并损害听觉功能，这与全身给药类似。我们在出生后第21天至31天接受庆大霉素或生理盐水鼻内冲洗的Sprague-Dawley大鼠中研究了这一推测。我们在第41天通过评估对宽带短声和纯音短音（4、8、16、24和32千赫）的脑干听觉诱发电位来检测听觉功能。我们发现暴露于庆大霉素的动物的听觉功能有显著变化。具体而言，暴露于庆大霉素的动物对短声和音短音的阈值显著更高。对于宽带短声，I至IV波的潜伏期没有变化。然而，我们发现，在对24千赫音短音的反应中，所有波的波潜伏期和波间潜伏期均显著延长。这些发现共同表明，经鼻内给予庆大霉素会导致听觉功能受损，这与其他给药途径一致。
