{
  "abstract": "Cadmium (Cd), a prevalent environmental contaminant, is associated with auditory dysfunction. The cochlear blood-labyrinth barrier (BLB) protects the inner ear from toxic substances, a process in which the ATP-binding cassette subfamily C member 1 protein, ABCC1, plays a critical role in expelling toxins from its cells. To understand the specific contribution of ABCC1 to Cd-induced hearing damage, we employed both an in vivo model (ABCC1 knockout mice, Abcc1 -/- mice) and an in vitro endothelial model (ABCC1-deficient human umbilical vein endothelial cells, ABCC1 -/-HUVECs). These models were exposed to CdCl₂ to assess auditory responses, histopathology, BLB integrity, and oxidative stress. We also explored the NOX2-ROS/PI3K-AKT pathway using immunofluorescence, Western blotting, and RNA-seq analyses. The results indicate that ABCC1 deficiency exacerbated Cd-induced BLB leakage, promoted spiral ganglion neurons and presynaptic ribbon puncta loss, and increased ABR thresholds. In both animal and cellular models, ABCC1 deficiency enhanced NOX2 expression, ROS accumulation, and AKT dephosphorylation. Significantly, pharmacological inhibition of NOX2 with GSK2795039 attenuated oxidative stress, preserved endothelial barrier function, and partially restored PI3K-AKT signaling. These findings identify ABCC1 as a critical protector of cochlear vascular integrity during Cd exposure, acting through the NOX2-ROS/PI3K-AKT axis, and suggest its potential as a therapeutic target for preventing Cd-induced hearing loss.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.",
    "Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan 410008, China.",
    "National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Changsha, Hunan 410008, China.",
    "Medical Functional Experiment Center, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan 410078, China.",
    "Xiangya School of Public Health, Central South University, Changsha, Hunan 410013, China.",
    "Furong Laboratory, Changsha, Hunan 410008, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Shuai Zhang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yongjia Chen"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Yijiang Bai"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Bo Pang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Mengzhu Jiang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Zequn Nie"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Huping Huang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Lu Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Jie Ling"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Tianhan Kai",
      "orcid": "0000-0001-5667-1426"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Lingyun Mei",
      "orcid": "0000-0003-3034-3322"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dqpdvgy8v6xb7.bib",
  "cited_by": 0,
  "doi": "10.1021/envhealth.6c00120",
  "fulltext_url": "https://europepmc.org/articles/PMC13681441",
  "id": "dqpdvgy8v6xb7",
  "issns": [
    "2833-8278"
  ],
  "landing_url": "https://europepmc.org/article/MED/42903442",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2809|Hearing, Cochlea, Tinnitus, Genetics"
    ]
  ],
  "openalex": "W7167624237",
  "pdf_url": "https://europepmc.org/articles/PMC13681441?pdf=render",
  "pmcid": "PMC13681441",
  "pmid": "42903442",
  "published": "2026-07-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dqpdvgy8v6xb7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:59Z",
      "native_id": "MED:42903442",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42903442"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2809|Hearing, Cochlea, Tinnitus, Genetics",
      "subfield": "neuroscience"
    }
  ],
  "title": "ABCC1 Deficiency Mediates Susceptibility to Cd-Induced Hearing Loss via the NOX2/ROS Axis.",
  "title_text": "ABCC1 Deficiency Mediates Susceptibility to Cd-Induced Hearing Loss via the NOX2/ROS Axis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:59Z",
  "url": "https://research.draconitic.com/paper/dqpdvgy8v6xb7",
  "venue": "Environment & health (Washington, D.C.)",
  "versions": []
}