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In vivo, we employed auditory brainstem response (ABR) testing and ribbon synapses counting to assess changes in mouse hearing function, and observed the morphology of hair cells through scanning electron microscopy. SRT1720 was administered to the cochlea via round window injection. In vitro, western blot analysis and RT\u2010qPCR were used, and Lenti\u2010shNrf2 was used to knockdown Nrf2 expression. In addition, various oxidative stress indicators were detected by immunofluorescence, kit\u2010based assays, and flow cytometry. ABR measurement of HHL mouse showed a significant increase in hearing threshold, as well as a decrease and delay in the I wave amplitude and latency on the first day after noise exposure. Histological observation showed a significant loss of ribbon synapses and stereocilia lodging. HHL mice exhibited oxidative stress, which was reduced by pretreatment with SRT1720. Additionally, SRT1720 could reduce hydrogen peroxide\u2010induced oxidative stress in HEI\u2010OC1 cells through activating the SIRT1\/Nrf2 pathway. Subsequent experiments with Nrf2 knockdown confirmed the importance of this pathway. findings highlight oxidative stress as the primary contributor to HHL, with the SIRT1\/Nrf2 signaling pathway emerging as a promising therapeutic target for alleviating HHL.<\/jats:p>","DOI":"10.1002\/cbin.12264","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T05:29:27Z","timestamp":1733117367000},"page":"262-276","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The potential role of the SIRT1\u2010Nrf2 signaling pathway in alleviating hidden hearing loss via antioxidant stress"],"prefix":"10.1002","volume":"49","author":[{"given":"Zeyu","family":"Zheng","sequence":"first","affiliation":[{"name":"Center of Clinical Aerospace Medicine, School of Aerospace Medicine, Key Laboratory of Aerospace Medicine of Ministry of Education Air Force Medical University Xi'an Shaanxi 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