{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T11:02:47Z","timestamp":1781780567074,"version":"3.54.5"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"an Italfarmaco S.p.A. research grant","award":["2022ZL4JP8"],"award-info":[{"award-number":["2022ZL4JP8"]}]},{"name":"an Italfarmaco S.p.A. research grant","award":["25788"],"award-info":[{"award-number":["25788"]}]},{"name":"the 2022 PRIN project","award":["2022ZL4JP8"],"award-info":[{"award-number":["2022ZL4JP8"]}]},{"name":"the 2022 PRIN project","award":["25788"],"award-info":[{"award-number":["25788"]}]},{"name":"the AIRC grant IG","award":["2022ZL4JP8"],"award-info":[{"award-number":["2022ZL4JP8"]}]},{"name":"the AIRC grant IG","award":["25788"],"award-info":[{"award-number":["25788"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Chemotherapy-induced peripheral neuropathy remains a significant side effect of cancer treatment, often requiring dose reductions or even discontinuation of therapy. Paclitaxel (PTX), a widely used chemotherapeutic agent for solid tumors, is particularly neurotoxic, and no effective treatment exists for paclitaxel-induced peripheral neuropathy (PIPN). Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histone and non-histone proteins, including transcription factors and cytoskeletal components. This study evaluates the HDAC6 inhibitor ITF6475 for its potential to prevent PIPN and compares its effects with ricolinostat, a well-established HDAC6 inhibitor previously studied in cisplatin-induced neuropathy models. Female C57BL\/6 mice received PTX vehicle (VEH) or PTX (70 mg\/kg intravenously, once per week for four weeks), and the remaining four groups received PTX with co-treatment of either ricolinostat (50 mg\/kg orally, daily) or ITF6475 (1, 6, or 12.5 mg\/kg orally, daily). Neurophysiological assessments at the end of treatment showed a significant reduction in caudal sensory nerve action potential amplitude across all PTX-treated groups compared to the VEH group. At the same time, PTX treatment led to the development of mechanical allodynia. However, co-treatment with the HDAC6 inhibitor prevented significant differences compared to the VEH group. PTX-induced reduction in intraepidermal nerve fiber density was significantly prevented in the PTX + ITF6475 (1 mg\/kg) group, and PTX-induced increase in neurofilament light levels was reduced in all ITF6475 co-treated groups. These findings support the potential of ITF6475 in preventing small fiber damage in a severe, chronic PIPN model.<\/jats:p>","DOI":"10.3390\/toxics13090767","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T10:27:12Z","timestamp":1757500032000},"page":"767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["ITF6475, a New Histone Deacetylase 6 Inhibitor, Prevents Painful Neuropathy Induced by Paclitaxel"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4128-2406","authenticated-orcid":false,"given":"Guido","family":"Cavaletti","sequence":"first","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"},{"name":"Fondazione IRCCS San Gerardo dei Tintori di Monza, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4946-647X","authenticated-orcid":false,"given":"Annalisa","family":"Canta","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3469-1829","authenticated-orcid":false,"given":"Alessia","family":"Chiorazzi","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6438-286X","authenticated-orcid":false,"given":"Eleonora","family":"Pozzi","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0963-7107","authenticated-orcid":false,"given":"Valentina","family":"Carozzi","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4281-4577","authenticated-orcid":false,"given":"Cristina","family":"Meregalli","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6106-6183","authenticated-orcid":false,"given":"Paola","family":"Alberti","sequence":"additional","affiliation":[{"name":"Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, 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Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8648-0660","authenticated-orcid":false,"given":"Barbara","family":"Vergani","sequence":"additional","affiliation":[{"name":"Preclinical R&D Department, Italfarmaco S.p.A., 20092 Cinisello Balsamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8341-9699","authenticated-orcid":false,"given":"Christian","family":"Steink\u00fchler","sequence":"additional","affiliation":[{"name":"Preclinical R&D Department, Italfarmaco S.p.A., 20092 Cinisello Balsamo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7597-7084","authenticated-orcid":false,"given":"Simonetta Andrea","family":"Licandro","sequence":"additional","affiliation":[{"name":"Preclinical R&D Department, Italfarmaco S.p.A., 20092 Cinisello Balsamo, 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