Abstract
Aminoglycoside antibiotics such as gentamicin could cause ototoxicity in mammalians, by inducing oxidative stress and apoptosis in sensory hair cells of the cochlea. Sodium hydrosulfide (NaHS) is reported to alleviate oxidative stress and apoptosis, but its role in protecting aminoglycoside-induced hearing loss is unclear. In this study, we investigated the anti-oxidant and anti-apoptosis effect of NaHS in in vitro cultured House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and isolated mouse cochlea. Results from cultured HEI-OC1 cells and cochlea consistently indicated that NaHS exhibited protective effects from gentamicin-induced ototoxicity, evident by maintained cell viability, hair cell number and cochlear morphology, reduced reactive oxygen species production and mitochondrial depolarization, as well as apoptosis activation of the intrinsic pathway. Moreover, in the isolated cochlear culture, NaHS was also demonstrated to protect the explant from gentamicin-induced mechanotransduction loss. Our study using multiple in vitro models revealed for the first time, the potential of NaHS as a therapeutic agent in protecting against aminoglycoside-induced hearing loss.
Highlights
In all mammals, hair cells are the sensory receptors of both the auditory and the vestibular system
First by using the gentamicin-insulted House Ear Institute-Organ of Corti 1 (HEI-OC1) cell model, we have established that gentamicin reduced cell viability and elevated cellular reactive oxygen species (ROS) production, which in turn triggered mitochondrial depolarization and activation of the intrinsic apoptotic pathway
Gentamicin was found to induce oxidative stress in hair cells that could eventually lead to apoptosis [7, 28, 31], which severely limited its clinical use
Summary
Hair cells are the sensory receptors of both the auditory and the vestibular system. The outer three rows consist of outer hair cells (OHCs), and they function as the cochlea's mechanotransduction amplifier. Sensorineural hearing loss is a prevalent worldwide health problem, and a significant proportion of hearing loss is caused by aminoglycoside-induced death of sensory hair cells [4]. Aminoglycosides, such as gentamicin, amikacin, kanamycin and neomycin, originate generally from Gram-negative bacteria and is able to inhibit protein synthesis [5].
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