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

endoplasmic reticulum stress hair cell hearing loss neomycin pitavastatin

Journal

Frontiers in molecular neuroscience
ISSN: 1662-5099
Titre abrégé: Front Mol Neurosci
Pays: Switzerland
ID NLM: 101477914

Informations de publication

Date de publication:
2022
Historique:
received: 07 06 2022
accepted: 13 07 2022
entrez: 22 8 2022
pubmed: 23 8 2022
medline: 23 8 2022
Statut: epublish

Résumé

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 unknown. The objectives of this 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 pretreatment 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.

Identifiants

DOI: 10.3389/fnmol.2022.963083 PMID: 35992197 PMC: PMC9381809
pubmed: 35992197
doi: 10.3389/fnmol.2022.963083
pmc: PMC9381809
doi:

Types de publication

Journal Article

Langues

eng

Pagination

963083

Informations de copyright

Copyright © 2022 Wu, Meng, Guan, Zhao, Zhang, Fang, Zhang, Sun, Cai, Huang, Yang, Yu, Cui, He and Chai.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Yunhao Wu (Y)

State Key Laboratory of Bioelectronics, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Department of Otolaryngology Head and Neck Surgery, School of Life Sciences and Technology, Zhongda Hospital, Advanced Institute for Life and Health, Southeast University, Nanjing, China.

Wei Meng (W)

Department of Otorhinolaryngology Head and Neck Surgery, School of Medicine, Nanjing Tongren Hospital, Southeast University, Nanjing, China.

Ming Guan (M)

Department of Otolaryngology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Xiaolong Zhao (X)

Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

Chen Zhang (C)

Beijing Key Laboratory of Neural Regeneration and Repair, Department of Neurobiology, Advanced Innovation Center for Human Brain Protection, School of Basic Medical Sciences, Capital Medical University, Beijing, China.

Qiaojun Fang (Q)

State Key Laboratory of Bioelectronics, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Department of Otolaryngology Head and Neck Surgery, School of Life Sciences and Technology, Zhongda Hospital, Advanced Institute for Life and Health, Southeast University, Nanjing, China.

Yuhua Zhang (Y)

State Key Laboratory of Bioelectronics, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Department of Otolaryngology Head and Neck Surgery, School of Life Sciences and Technology, Zhongda Hospital, Advanced Institute for Life and Health, Southeast University, Nanjing, China.

Zihui Sun (Z)

Department of Otorhinolaryngology Head and Neck Surgery, School of Medicine, Nanjing Tongren Hospital, Southeast University, Nanjing, China.

Mingjing Cai (M)

Department of Otorhinolaryngology Head and Neck Surgery, School of Medicine, Nanjing Tongren Hospital, Southeast University, Nanjing, China.

Dongdong Huang (D)

Department of Otorhinolaryngology Head and Neck Surgery, School of Medicine, Nanjing Tongren Hospital, Southeast University, Nanjing, China.

Xuechun Yang (X)

Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Yafeng Yu (Y)

Department of Otolaryngology, First Affiliated Hospital of Soochow University, Suzhou, China.

Yong Cui (Y)

Department of Otolaryngology-Head and Neck Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
The Second School of Clinical Medicine, South Medical University, Guangzhou, China.
School of Medicine, South China University of Technology, Guangzhou, China.

Shuangba He (S)

Department of Otorhinolaryngology Head and Neck Surgery, School of Medicine, Nanjing Tongren Hospital, Southeast University, Nanjing, China.

Renjie Chai (R)

State Key Laboratory of Bioelectronics, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Department of Otolaryngology Head and Neck Surgery, School of Life Sciences and Technology, Zhongda Hospital, Advanced Institute for Life and Health, Southeast University, Nanjing, China.
Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China.

Classifications MeSH