AUTHOR=Wu Yunhao , Meng Wei , Guan Ming , Zhao Xiaolong , Zhang Chen , Fang Qiaojun , Zhang Yuhua , Sun Zihui , Cai Mingjing , Huang Dongdong , Yang Xuechun , Yu Yafeng , Cui Yong , He Shuangba , Chai Renjie 

TITLE=Pitavastatin protects against neomycin-induced ototoxicity through inhibition of endoplasmic reticulum stress

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 15 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2022.963083

DOI=10.3389/fnmol.2022.963083

ISSN=1662-5099

ABSTRACT=Irreversible injury to inner ear hair cells induced by aminoglycoside antibiotics contributes to the formation of sensorineural hearing loss. Pitavastatin (PTV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been reported to exert neuroprotective effects. However, its role in aminoglycoside-induced hearing loss remains unknow. The objectives of the present study were to investigate the beneficial effects as well as the mechanism of action of PTV against neomycin-induced ototoxicity. We found that PTV remarkably reduced hair cell loss in mouse cochlear explants and promoted auditory HEI-OC1 cells survival after neomycin stimulation. We also observed that the auditory brainstem response threshold that was increased by neomycin was significantly reduced by pre-treatment with PTV in mice. Furthermore, neomycin-induced endoplasmic reticulum stress in hair cells was attenuated by PTV treatment through inhibition of PERK/eIF2α/ATF4 signaling. Additionally, we found that PTV suppressed the RhoA/ROCK/JNK signal pathway which was activated by neomycin stimulation in HEI-OC1 cells. Collectively, our results showed that PTV might serve as a promising therapeutic agent against aminoglycoside-induced ototoxicity.