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

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.