Paeoniflorin reduces neomycin-induced ototoxicity in hair cells by suppression of reactive oxygen species generation and extracellularly regulated kinase signalization

Xiaoyu Yu; Zhaomin Fan; Yuechen Han; Daogong Zhang; Lei Xu; Mingming Wang; Qianqian Yang; Hongrui Li; Meijuan Zhou; Lili Zhang; Gaoying Sun; Xiaohui Bai; Jianfeng Li; Haibo Wang

doi:10.1016/j.toxlet.2017.12.026

Paeoniflorin reduces neomycin-induced ototoxicity in hair cells by suppression of reactive oxygen species generation and extracellularly regulated kinase signalization

Toxicol Lett. 2018 Mar 15:285:9-19. doi: 10.1016/j.toxlet.2017.12.026. Epub 2017 Dec 29.

Authors

Xiaoyu Yu¹, Zhaomin Fan¹, Yuechen Han², Daogong Zhang², Lei Xu², Mingming Wang², Qianqian Yang³, Hongrui Li³, Meijuan Zhou³, Lili Zhang³, Gaoying Sun³, Xiaohui Bai³, Jianfeng Li⁴, Haibo Wang⁵

Affiliations

¹ Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; Shandong Provincial Key Laboratory of Otology, Jinan, China; Shandong Institute of Otolaryngology, Jinan, China.
² Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
³ Shandong Provincial Key Laboratory of Otology, Jinan, China; Shandong Institute of Otolaryngology, Jinan, China.
⁴ Shandong Provincial Key Laboratory of Otology, Jinan, China; Shandong Institute of Otolaryngology, Jinan, China. Electronic address: lijianfeng@hotmail.com.
⁵ Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China; Shandong Provincial Key Laboratory of Otology, Jinan, China; Shandong Institute of Otolaryngology, Jinan, China. Electronic address: whboto11@163.com.

PMID: 29292089
DOI: 10.1016/j.toxlet.2017.12.026

Abstract

The present study was designed to investigate the effect of paeoniflorin (PF) on neomycin-induced ototoxicity in hair cells (HCs). Here, we took advantage of C57BL/6 mice and cochlear explants culture to determine the role of PF in vivo and in vitro. We demonstrated that neomycin exposure induced severe hearing loss and HC damage, which was mediated by activated mitochondrial apoptosis pathway, promoted extracellular signal-regulated kinase (ERK) signaling as well as enhanced reactive oxygen species (ROS) generation in HCs. Interestingly, we found that PF pretreatment significantly alleviated neomycin-induced hearing loss, attenuated HC injury and decreased HC apoptosis caused by neomycin. Mechanistic studies revealed that PF could decrease cellular ROS levels, suppress the activation of ERK signaling and, subsequently, mitigate the imbalance of mitochondrial apoptotic pathway, thus protecting HCs from neomycin-induced apoptosis. This study indicates that PF may serve as an antioxidative and anti-apoptotic agent to prevent hearing loss caused by neomycin.

Keywords: Apoptosis; MAPK; Neomycin; Ototoxicity; Paeoniflorin; ROS.

MeSH terms

Animals
Antioxidants / administration & dosage
Antioxidants / therapeutic use*
Apoptosis / drug effects
Cells, Cultured
Evoked Potentials, Auditory, Brain Stem / drug effects
Extracellular Signal-Regulated MAP Kinases / metabolism*
Glucosides / administration & dosage
Glucosides / therapeutic use*
Hair Cells, Auditory / drug effects*
Hair Cells, Auditory / metabolism
Hair Cells, Auditory / pathology
Hearing Loss / chemically induced
Hearing Loss / metabolism
Hearing Loss / pathology
Hearing Loss / prevention & control*
Mice, Inbred C57BL
Mitochondria / drug effects
Mitochondria / pathology
Monoterpenes / administration & dosage
Monoterpenes / therapeutic use*
Neomycin / toxicity*
Reactive Oxygen Species / metabolism*
Signal Transduction

Substances

Antioxidants
Glucosides
Monoterpenes
Reactive Oxygen Species
peoniflorin
Extracellular Signal-Regulated MAP Kinases
Neomycin