Unveiling a Novel Mechanism in Noise-Induced Hearing Loss: Oxeiptosis-Mediated Regulated Cell Death of Cochlear Hair Cell

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.