Treatment with the Ferroptosis Inhibitor Ferrostatin‐1 Attenuates Noise‐Induced Hearing Loss by Suppressing Ferroptosis and Apoptosis

作者：Pengwei Ma, Wei‐Long Wang, Jiawei Chen, Hao Yuan, Peiheng Lu, Wei Gao, Xuerui Ding, Yu-Qiang Lun, Rui Liang, Zuhong He, Qian Yang, Lianjun Lu · 发表于：Oxidative Medicine and Cellular Longevity · 年份：2022 · DOI：10.1155/2022/3373828 · 被引用次数：41 · 研究领域：Hearing, Cochlea, Tinnitus, Genetics、Cancer-related molecular mechanisms research、Inflammasome and immune disorders

Hair cell death induced by excessive reactive oxygen species (ROS) has been identified as the major pathogenesis of noise-induced hearing loss (NIHL). Recent studies have demonstrated that cisplatin- and neomycin-induced ototoxicity can be alleviated by ferroptosis inhibitors. However, whether ferroptosis inhibitors have a protective effect against NIHL remains unknown. We investigated the protective effect of the ferroptosis inhibitor ferrostatin-1 (Fer-1) on NIHL in vivo in CBA/J mice and investigated the protective effect of Fer-1 on tert-butyl hydroperoxide (TBHP)-induced hair cell damage in vitro in cochlear explants and HEI-OC1 cells. We observed ROS overload and lipid peroxidation, which led to outer hair cell (OHC) apoptosis and ferroptosis, in the mouse cochlea after noise exposure. The expression level of apoptosis-inducing factor mitochondria-associated 2 (AIFM2) was substantially increased following elevation of the expression of its upstream protein P53 after noise exposure. The ferroptosis inhibitor Fer-1was demonstrated to enter the inner ear after the systemic administration. Administration of Fer-1 significantly alleviated noise-induced auditory threshold elevation and reduced the loss of OHCs, inner hair cell (IHC) ribbon synapses, and auditory nerve fibers (ANFs) caused by noise. Mechanistically, Fer-1 significantly reduced noise- and TBHP-induced lipid peroxidation and iron accumulation in hair cells, alleviating ferroptosis in cochlear cells consequently....