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Recent studies have demonstrated that cisplatin\u2010 and neomycin\u2010induced 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\u20101 (Fer\u20101) on NIHL in vivo in CBA\/J mice and investigated the protective effect of Fer\u20101 on tert\u2010butyl hydroperoxide (TBHP)\u2010induced hair cell damage in vitro in cochlear explants and HEI\u2010OC1 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\u2010inducing factor mitochondria\u2010associated 2 (AIFM2) was substantially increased following elevation of the expression of its upstream protein P53 after noise exposure. The ferroptosis inhibitor Fer\u20101was demonstrated to enter the inner ear after the systemic administration. Administration of Fer\u20101 significantly alleviated noise\u2010induced 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\u20101 significantly reduced noise\u2010 and TBHP\u2010induced lipid peroxidation and iron accumulation in hair cells, alleviating ferroptosis in cochlear cells consequently. Furthermore, Fer\u20101 treatment decreased the levels of TfR1, P53, and AIFM2. These results suggest that Fer\u20101 exerted its protective effects by scavenging of ROS and inhibition of TfR1\u2010mediated ferroptosis and P53\u2010AIFM2 signaling pathway\u2010mediated apoptosis. Our findings suggest that Fer\u20101 is a promising drug for treating NIHL because of its ability to inhibit noise\u2010induced hair cell apoptosis and ferroptosis, opening new avenues for the treatment of NIHL.<\/jats:p>","DOI":"10.1155\/2022\/3373828","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T11:48:45Z","timestamp":1670413725000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Treatment with the Ferroptosis Inhibitor Ferrostatin\u20101 Attenuates Noise\u2010Induced Hearing Loss by Suppressing Ferroptosis and 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