Xinyu Zhang1  · Meihao Qi1  · Peng Zhang1  · Zejun Gao1  · Ziqi Wu1  · Wenyue Wang1  · Runqin Yang1  · Xiaogang An1  · Fei Lu1  · Renfeng Wang1  · Qingwen Zhu1,2 · Dingjun Zha1

1 Department of Otolaryngology‑Head and Neck Surgery, Xijing Hospital, Air Force Medical University, Xi’an 710032, China 

2 Department of Otolaryngology‑Head and Neck Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China

Abstract

Noise-induced hearing loss is a prevalent form of sensorineural hearing impairment that negatively impacts quality of life and has no effective clinical treatments. Damage due to oxidative stress in cochlear hair cells is thought to be the typical pathological basis. Oxeiptosis is oxidative stress-induced, caspase-independent modality of cell death. In this study, we found that oxeiptosis plays an important role in noise-induced hearing loss, which has not been previously identified. Using protein quantification, protein-protein interaction studies, and immunofluorescence staining in cellular models, we elucidated the pivotal molecules of oxeiptosis. Building on the in vitro experimental data, we detected characteristic protein alterations along the oxeiptosis pathway in noise-induced hearing loss murine models. Furthermore, the pharmacological suppression effectively attenuated noise-induced oxeiptosis in cochlear hair cells and partially alleviated hair cell death. This study confirms the existence of a new cell death pathway in NIHL and provides a potential treatment alternative.

Keywords

Oxeiptosis; Oxidative stress; Hearing loss; Noise

[SpringerLink]