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慢性口服司来吉兰治疗可减轻 BALB/c 小鼠的年龄相关性听力损失。

Chronic Oral Selegiline Treatment Mitigates Age-Related Hearing Loss in BALB/c Mice.

机构信息

Department of Pharmacology and Pharmacotherapy, Semmelweis University, H-1089 Budapest, Hungary.

Department of Otorhinolaryngology, Head and Neck Surgery, Semmelweis University, H-1083 Budapest, Hungary.

出版信息

Int J Mol Sci. 2021 Mar 11;22(6):2853. doi: 10.3390/ijms22062853.

Abstract

Age-related hearing loss (ARHL), a sensorineural hearing loss of multifactorial origin, increases its prevalence in aging societies. Besides hearing aids and cochlear implants, there is no FDA approved efficient pharmacotherapy to either cure or prevent ARHL. We hypothesized that selegiline, an antiparkinsonian drug, could be a promising candidate for the treatment due to its complex neuroprotective, antioxidant, antiapoptotic, and dopaminergic neurotransmission enhancing effects. We monitored by repeated Auditory Brainstem Response (ABR) measurements the effect of chronic per os selegiline administration on the hearing function in BALB/c and DBA/2J mice, which strains exhibit moderate and rapid progressive high frequency hearing loss, respectively. The treatments were started at 1 month of age and lasted until almost a year and 5 months of age, respectively. In BALB/c mice, 4 mg/kg selegiline significantly mitigated the progression of ARHL at higher frequencies. Used in a wide dose range (0.15-45 mg/kg), selegiline had no effect in DBA/2J mice. Our results suggest that selegiline can partially preserve the hearing in certain forms of ARHL by alleviating its development. It might also be otoprotective in other mammals or humans.

摘要

年龄相关性听力损失(ARHL)是一种多因素起源的感觉神经性听力损失,在老龄化社会中其发病率不断增加。除了助听器和人工耳蜗植入物外,目前还没有 FDA 批准的有效药物疗法可以治愈或预防 ARHL。我们假设,由于其复杂的神经保护、抗氧化、抗细胞凋亡和多巴胺能神经传递增强作用,抗帕金森病药物司来吉兰可能是治疗 ARHL 的有前途的候选药物。我们通过重复听觉脑干反应(ABR)测量来监测慢性口服司来吉兰给药对 BALB/c 和 DBA/2J 小鼠听力功能的影响,这两种品系分别表现出中度和快速进展的高频听力损失。治疗分别从 1 个月大开始,持续到近 10 个月和 5 个月大。在 BALB/c 小鼠中,4mg/kg 的司来吉兰可显著减轻高频 ARHL 的进展。司来吉兰在较宽的剂量范围内(0.15-45mg/kg)使用时,对 DBA/2J 小鼠没有影响。我们的研究结果表明,司来吉兰通过减轻 ARHL 的发展,可部分保护某些形式的 ARHL 的听力。它在其他哺乳动物或人类中也可能具有耳保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7231/7999597/17460011694b/ijms-22-02853-g001.jpg

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