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NaHS Protects Cochlear Hair Cells from Gentamicin-Induced Ototoxicity by Inhibiting the Mitochondrial Apoptosis
Yaodong Dong1, Dongliang Liu1, Yue Hu1
1Department of Otology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, Liaoning, China.
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.
Insights
Sodium hydrosulfide (NaHS) protects against gentamicin-induced ototoxicity. This study shows NaHS preserves hair cell function and viability, offering potential for preventing aminoglycoside-induced hearing loss.
Area of Science:
- Ototoxicity
- Pharmacology
- Cell Biology
Background:
- Aminoglycoside antibiotics, like gentamicin, can cause ototoxicity by damaging cochlear sensory hair cells through oxidative stress and apoptosis.
- The protective role of sodium hydrosulfide (NaHS) against aminoglycoside-induced hearing loss remains largely unexplored.
Purpose of the Study:
- To investigate the antioxidant and anti-apoptotic effects of NaHS in protecting against gentamicin-induced ototoxicity in vitro.
- To evaluate NaHS's potential as a therapeutic agent for preventing hearing loss caused by aminoglycoside antibiotics.
Main Methods:
- Utilized in vitro cultured House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and isolated mouse cochlea models.
- Assessed cell viability, hair cell number, cochlear morphology, reactive oxygen species (ROS) production, mitochondrial depolarization, and apoptosis.
- Measured mechanotransduction function in isolated cochlear explants.
Main Results:
- NaHS demonstrated significant protective effects against gentamicin-induced ototoxicity in both HEI-OC1 cells and mouse cochlea.
- NaHS treatment maintained cell viability, hair cell number, and cochlear morphology.
- Reduced ROS production, mitochondrial depolarization, and apoptosis were observed, alongside preserved mechanotransduction in cochlear explants.
Conclusions:
- NaHS exhibits potent antioxidant and anti-apoptotic properties that protect against gentamicin-induced ototoxicity.
- NaHS preserves cochlear hair cell function and viability, indicating its potential as a therapeutic strategy for preventing aminoglycoside-induced hearing loss.
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