{
    "abstract": "This study examined the effect of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an anion channel blocker of voltage-dependent anion channel 1 (VDAC1), on noise-induced hearing loss (NIHL) and its underlying mechanisms.\nCochlear explants and House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were used to assess the effect of DIDS in\u00a0vitro. Auditory brainstem responses were used to assess auditory functions in mice. Immunofluorescence staining of myosin 7a and CTBP2 were used to examine hair cells and synaptic ribbons. The accumulation of reactive oxygen species (ROS) was measured by 4-HNE staining. The gene expression changes of cochlea were analyzed using RNA sequencing.\nDIDS reduced the levels of ROS in cochlear explants and attenuated cell death caused by hydrogen peroxide in both cochlear explants and HEI-OC1 cells. In C57BL/6 mice, DIDS reduced ROS generation and tumor necrosis factor-\u03b1 induced by noise exposure, thereby protecting outer hair cells and inner hair cell synaptic ribbons from noise-induced damage through a mechanism involving the PINK1/Parkin signaling pathway. The preventive effect of DIDS in cochlear explants was eliminated by mitophagy inhibition.\nVDAC1 inhibition enhances mitophagy in cochlear hair cells, playing a critical role in defending against oxidative stress and inflammation. Downregulation of VDAC1 may thus be considered a therapeutic strategy for preventing cochlear hair cell damage and reducing NIHL.",
    "authors": [
        {
            "affiliation": "Shanghai Key Laboratory of Sleep Disordered Breathing, Department of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
            "firstname": "Yuchen",
            "initials": "Y",
            "lastname": "Jin"
        },
        {
            "affiliation": "Shanghai Key Laboratory of Sleep Disordered Breathing, Department of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
            "firstname": "Wenqi",
            "initials": "W",
            "lastname": "Dong"
        },
        {
            "affiliation": "Shanghai Key Laboratory of Sleep Disordered Breathing, Department of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
            "firstname": "Yumeng",
            "initials": "Y",
            "lastname": "Jiang"
        },
        {
            "affiliation": "Shanghai Key Laboratory of Sleep Disordered Breathing, Department of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
            "firstname": "Lingkang",
            "initials": "L",
            "lastname": "Dong"
        },
        {
            "affiliation": "Department of Otolaryngology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.",
            "firstname": "Zhuangzhuang",
            "initials": "Z",
            "lastname": "Li"
        },
        {
            "affiliation": "Shanghai Key Laboratory of Sleep Disordered Breathing, Department of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
            "firstname": "Dongzhen",
            "initials": "D",
            "lastname": "Yu"
        }
    ],
    "conclusions": "VDAC1 inhibition enhances mitophagy in cochlear hair cells, playing a critical role in defending against oxidative stress and inflammation. Downregulation of VDAC1 may thus be considered a therapeutic strategy for preventing cochlear hair cell damage and reducing NIHL.",
    "copyrights": "\u00a9 2025 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.",
    "doi": "10.1111/cns.70410\n10.1002/ar.22598\n10.7717/peerj.14514\n10.1186/s12974-022-02585-w\n10.1002/jnr.24426\n10.1038/s41467-024-54681-5\n10.1002/advs.202402671\n10.1016/s0140-6736(23)02874-x\n10.3389/fnins.2022.867453\n10.1016/j.ymthe.2024.02.029\n10.2471/blt.21.285643\n10.5271/sjweh.2887\n10.1523/jneurosci.2845-09.2009\n10.1002/14651858.CD006396.pub4\n10.1097/mao.0000000000001071\n10.1038/s41388-023-02907-z\n10.3390/antiox8040109\n10.1080/15548627.2022.2062872\n10.3389/fncel.2023.1140916\n10.1016/j.mam.2010.03.002\n10.1080/15548627.2020.1841953\n10.1111/acel.13663\n10.1016/j.exer.2021.108640\n10.1159/000369728\n10.1016/j.bcp.2023.115440\n10.1016/j.bcp.2021.114904\n10.1038/s41467-020-16113-y\n10.1073/pnas.2221744120\n10.1038/s41598-019-50506-4\n10.1007/s12264-020-00624-1\n10.1089/ars.2014.6004\n10.1038/srep19329\n10.1074/jbc.RA118.003044\n10.1523/jneurosci.2282-12.2013\n10.1016/j.ecoenv.2022.113992\n10.1016/j.freeradbiomed.2021.11.020\n10.1016/j.immuni.2022.06.007\n10.3390/ijms21082692\n10.1121/1.5132545\n10.1080/15548627.2023.2182482\n10.3389/fncel.2019.00550\n10.3389/fphys.2017.00460\n10.1016/j.cmet.2018.09.008\n10.1016/j.ejphar.2021.174662\n10.1089/ars.2021.0283\n10.1016/j.heares.2013.01.006\n10.1016/j.heares.2016.11.013\n10.1007/s12035-023-03491-9\n10.3390/cells11193174\n10.1126/science.1161302\n10.1016/j.immuni.2023.03.003\n10.1038/s12276-022-00729-9\n10.1002/advs.202410550\n10.1016/j.pestbp.2024.106129\n10.1186/s40035-022-00329-7\n10.1016/j.ymthe.2021.06.024\n10.1186/s12974-022-02414-0\n10.1038/cdd.2012.81\n10.1016/j.molcel.2018.03.012\n10.1038/s41467-023-42829-8\n10.1038/s41598-019-46657-z\n10.7150/thno.79876\n10.1126/scitranslmed.aao0935\n10.1186/s12951-020-00709-z\n10.1002/advs.202305215",
    "journal": "CNS neuroscience & therapeutics",
    "keywords": [
        "4,4\u2032\u2010Diisothiocyanostilbene\u20102,2\u2032\u2010disulfonic acid",
        "autophagy",
        "hair cell",
        "noise\u2010induced hearing loss",
        "reactive oxygen species"
    ],
    "methods": null,
    "publication_date": "2025-04-26",
    "pubmed_id": "40285415\n23045252\n36743950\n36096817\n30950547\n39638804\n39206719\n38280389\n35685768\n38414247\n33953438\n20024522\n19906956\n28685503\n27518135\n38081963\n31022870\n35471096\n36909283\n20346371\n33124469\n35801276\n34058229\n25591913\n36720354\n34971589\n32404924\n37339214\n31575916\n33415566\n25694169\n26776972\n29739855\n23447610\n35994911\n34801666\n35835107\n32294929\n31795714\n36803235\n31920551\n28713289\n30293774\n34861207\n35708118\n23361190\n27916698\n37458989\n36231136\n18755977\n37001519\n35145201\n39556713\n39477583\n36578022\n34217890\n35227273\n22743996\n29656925\n37957156\n31300716\n36632220\n30842313\n33087104\n27109196\n37927600\n37984871",
    "results": "DIDS reduced the levels of ROS in cochlear explants and attenuated cell death caused by hydrogen peroxide in both cochlear explants and HEI-OC1 cells. In C57BL/6 mice, DIDS reduced ROS generation and tumor necrosis factor-\u03b1 induced by noise exposure, thereby protecting outer hair cells and inner hair cell synaptic ribbons from noise-induced damage through a mechanism involving the PINK1/Parkin signaling pathway. The preventive effect of DIDS in cochlear explants was eliminated by mitophagy inhibition.",
    "title": "VDAC1 Inhibition Protects Against Noise-Induced Hearing Loss via the PINK1/Parkin Pathway.",
    "xml": "<Element 'PubmedArticle' at 0x788502ef0360>"
}