Evidence map›Paper›PMID 42908325›Full record

ArticleCNS neuroscience & therapeutics2026

Interferon-γ Mitigates Oxaliplatin-Induced Neurotoxicity: Analogies With Connexin 43.

Alessandra Toti, Valentina Ferrara, Elena Lucarini, Laura Micheli, Clara Ciampi, Francesco Margiotta, Daniel Venturi, Carmen Parisio, Elisabetta Gerace, Lorenzo Curti and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Alessandra TotiDepartment of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.ORCID https://orcid.org/0000-0002-8435-6017
Valentina FerraraDepartment of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.ORCID https://orcid.org/0000-0002-7926-5479
Elena LucariniDepartment of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.ORCID https://orcid.org/0000-0002-3459-2660
Laura MicheliDepartment of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.ORCID https://orcid.org/0000-0002-6806-3222
Clara CiampiDepartment of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.ORCID https://orcid.org/0000-0002-6455-2723
Francesco MargiottaDepartment of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.ORCID https://orcid.org/0000-0002-6608-5399
Daniel VenturiDepartment of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.ORCID https://orcid.org/0009-0006-3933-0236
Carmen ParisioDepartment of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.ORCID https://orcid.org/0000-0003-0746-0774
Elisabetta GeraceDepartment of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.ORCID https://orcid.org/0000-0001-8448-6092
Lorenzo CurtiDepartment of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.ORCID https://orcid.org/0000-0001-9942-4193
Alessio MasiDepartment of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.ORCID https://orcid.org/0000-0002-0361-0950
Tommaso MelloClinical Gastroenterology Unit, Department of Biomedical Clinical and Experimental Sciences "Mario Serio", University of Florence, Florence, Italy.ORCID https://orcid.org/0000-0002-6192-6902
Guido MannaioniDepartment of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.ORCID https://orcid.org/0000-0002-8273-7377
Carla GhelardiniDepartment of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.ORCID https://orcid.org/0000-0001-9856-8144
Lorenzo Di Cesare MannelliDepartment of Neuroscience, Psychology, Drug Research and Child Health-NEUROFARBA-Pharmacology and Toxicology Section, University of Florence, Florence, Italy.ORCID https://orcid.org/0000-0001-8374-4432

Funding

Italian Ministry of University and Research (MIUR) 58514_DIPECC_23_27MNESYS PE00000006National Recovery and Resilience Plan (NRRP)Tuscany Region
6 · The paper itself

Abstract

aimsChemotherapy-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).

methodsRat 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.

resultsIFN-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.

conclusionIFN-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.

Indexed as

Antineoplastic AgentsConnexin 43Interferon-gammaNeuroprotective AgentsOrganoplatinum CompoundsOxaliplatinAnimalsDose-Response Relationship, DrugNeuronsRatsRats, Sprague-DawleySpinal CordAntineoplastic AgentsConnexin 43Interferon-gammaNeuroprotective AgentsOrganoplatinum CompoundsOxaliplatinhemichannelsIFN‐γ dualismneuropathyneurotrophic factorspro‐inflammatory cytokinespinal cord

Identifiers

PMID42908325
PMCPMC13687928

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