{
  "abstract": "Aims\n\nChemotherapy-induced neuropathy is a major side effect of platinum-based drugs such as oxaliplatin. Given the context-dependent pro-inflammatory or neuroprotective actions of interferon-γ (IFN-γ), this study investigated its role in an in vitro model of oxaliplatin-induced neurotoxicity (OIPN).Methods\n\nRat organotypic spinal cord slices were exposed to oxaliplatin to model chemotherapy-induced neurotoxicity responses in vitro. IFN-γ cytotoxicity was assessed at 6 and 24 h. Neurotoxicity, inflammatory mediators, neurotrophic factors, and markers of glial and neuronal activation were analyzed by biochemical and immunohistochemical assays. Connexin 43 (Cx43) was assessed using Gap19 and Gap27 to probe hemichannel and gap-junction contributions. Electrophysiological recordings characterized neuronal excitability.Results\n\nIFN-γ (6.5-200 ng/mL) was non-toxic and, at 65 ng/mL, significantly reduced oxaliplatin-induced neurotoxicity, decreasing LDH release and suppressing pro-inflammatory mediators (CCL2, SerpinA3N, CGRP, substance P, c-Fos). IFN-γ modulated its signaling by reducing IFNγR and increasing IRF1 expression. It prevented oxaliplatin-induced overexpression of neurotrophic factors and reduced glial and neuronal hyperactivation markers, preserving neuronal integrity. IFN-γ reduced Cx43 expression and hemichannel activity, and Gap19 reproduced selected protective effects. Electrophysiology showed attenuation of oxaliplatin-induced neuronal hyperexcitability.Conclusion\n\nIFN-γ attenuates oxaliplatin-induced neurotoxic responses in an in vitro spinal cord model. The parallel reduction in Cx43 expression and hemichannel activity supports further investigation of Cx43 signaling as a candidate pharmacological target in OIPN.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.",
    "European Biomedical Research Institute of Salerno (EBRIS), Salerno, Italy.",
    "Department of Health Science, University of Florence, Florence, Italy.",
    "Clinical Gastroenterology Unit, Department of Biomedical Clinical and Experimental Sciences \"Mario Serio\", University of Florence, Florence, Italy."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Alessandra Toti",
      "orcid": "0000-0002-8435-6017"
    },
    {
      "affs": [
        0
      ],
      "name": "Valentina Ferrara",
      "orcid": "0000-0002-7926-5479"
    },
    {
      "affs": [
        0
      ],
      "name": "Elena Lucarini",
      "orcid": "0000-0002-3459-2660"
    },
    {
      "affs": [
        0
      ],
      "name": "Laura Micheli",
      "orcid": "0000-0002-6806-3222"
    },
    {
      "affs": [
        0
      ],
      "name": "Clara Ciampi",
      "orcid": "0000-0002-6455-2723"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Francesco Margiotta",
      "orcid": "0000-0002-6608-5399"
    },
    {
      "affs": [
        0
      ],
      "name": "Daniel Venturi",
      "orcid": "0009-0006-3933-0236"
    },
    {
      "affs": [
        0
      ],
      "name": "Carmen Parisio",
      "orcid": "0000-0003-0746-0774"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Elisabetta Gerace",
      "orcid": "0000-0001-8448-6092"
    },
    {
      "affs": [
        0
      ],
      "name": "Lorenzo Curti",
      "orcid": "0000-0001-9942-4193"
    },
    {
      "affs": [
        0
      ],
      "name": "Alessio Masi",
      "orcid": "0000-0002-0361-0950"
    },
    {
      "affs": [
        3
      ],
      "name": "Tommaso Mello",
      "orcid": "0000-0002-6192-6902"
    },
    {
      "affs": [
        0
      ],
      "name": "Guido Mannaioni",
      "orcid": "0000-0002-8273-7377"
    },
    {
      "affs": [
        0
      ],
      "name": "Carla Ghelardini",
      "orcid": "0000-0001-9856-8144"
    },
    {
      "affs": [
        0
      ],
      "name": "Lorenzo Di Cesare Mannelli",
      "orcid": "0000-0001-8374-4432"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2d1q6aa4kat4y.bib",
  "cited_by": 0,
  "doi": "10.1002/cns.71197",
  "fulltext_url": "https://europepmc.org/articles/PMC13687928",
  "id": "2d1q6aa4kat4y",
  "issns": [
    "1755-5930",
    "1755-5949"
  ],
  "landing_url": "https://europepmc.org/article/MED/42908325",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Cancer Treatment and Pharmacology"
    ]
  ],
  "openalex": "W7223181678",
  "pdf_url": "https://europepmc.org/articles/PMC13687928?pdf=render",
  "pmcid": "PMC13687928",
  "pmid": "42908325",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2d1q6aa4kat4y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42908325",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42908325"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Treatment and Pharmacology",
      "subfield": "oncology"
    }
  ],
  "title": "Interferon-γ Mitigates Oxaliplatin-Induced Neurotoxicity: Analogies With Connexin 43.",
  "title_text": "Interferon-γ Mitigates Oxaliplatin-Induced Neurotoxicity: Analogies With Connexin 43.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:57Z",
  "url": "https://research.draconitic.com/paper/2d1q6aa4kat4y",
  "venue": "CNS neuroscience & therapeutics",
  "versions": []
}