{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:35:29Z","timestamp":1790202929557,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades, Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER), Uni\u00f3n Europea","award":["PI1800645"],"award-info":[{"award-number":["PI1800645"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Chemotherapy-induced peripheral neuropathy constitutes an unresolved clinical problem that severely decreases the quality of the patient\u2019s life. It is characterized by somatosensory alterations, including chronic pain, and a high risk of suffering mental disorders such as depression and anxiety. Unfortunately, an effective treatment for this neuropathology is yet to be found. We investigated the therapeutic potential of cobalt protoporphyrin IX (CoPP), a heme oxygenase 1 inducer, and morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate dichloromethane complex (GYY4137), a slow hydrogen sulfide (H2S) donor, in a preclinical model of paclitaxel (PTX)-induced peripheral neuropathy (PIPN) in mice. At three weeks after PTX injection, we evaluated the effects of the repetitive administration of 5 mg\/kg of CoPP and 35 mg\/kg of GYY4137 on PTX-induced nociceptive symptoms (mechanical and cold allodynia) and on the associated emotional disturbances (anxiety- and depressive-like behaviors). We also studied the mechanisms that could mediate their therapeutic properties by evaluating the expression of key proteins implicated in the development of nociception, oxidative stress, microglial activation, and apoptosis in prefrontal cortex (PFC) and dorsal root ganglia (DRG) of mice with PIPN. Results demonstrate that CoPP and GYY4137 treatments inhibited both the nociceptive symptomatology and the derived emotional alterations. These actions were mainly mediated through potentiation of antioxidant responses and inhibiting oxidative stress in the DRG and\/or PFC of mice with PIPN. Both treatments normalized some plasticity changes and apoptotic reactions, and GYY4137 blocked microglial activation induced by PTX in PFC. In conclusion, this study proposes CoPP and GYY4137 as good candidates for treating neuropathic pain, anxiety- and depressive-like effects of PTX.<\/jats:p>","DOI":"10.3390\/antiox11010122","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T01:15:26Z","timestamp":1641518126000},"page":"122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Beneficial Effects of Heme Oxygenase 1 and Hydrogen Sulfide Activation in the Management of Neuropathic Pain, Anxiety- and Depressive-like Effects of Paclitaxel in Mice"],"prefix":"10.3390","volume":"11","author":[{"given":"Gerard","family":"Roch","sequence":"first","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"},{"name":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Batall\u00e9","sequence":"additional","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"},{"name":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7283-3189","authenticated-orcid":false,"given":"Xue","family":"Bai","sequence":"additional","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"},{"name":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enric","family":"Pouso-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"},{"name":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"},{"name":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4621-8457","authenticated-orcid":false,"given":"Olga","family":"Pol","sequence":"additional","affiliation":[{"name":"Grup de Neurofarmacologia Molecular, Institut d\u2019Investigaci\u00f3 Biom\u00e8dica Sant Pau, Hospital de la Santa Creu i Sant Pau, 08041 Barcelona, Spain"},{"name":"Grup de Neurofarmacologia Molecular, Institut de Neuroci\u00e8ncies, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1093\/bja\/aex229","article-title":"Clinical and preclinical perspectives on Chemotherapy-Induced Peripheral Neuropathy (CIPN): A narrative review","volume":"119","author":"Flatters","year":"2017","journal-title":"Br. 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