{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:19:29Z","timestamp":1793830769272,"version":"4.6.1"},"reference-count":82,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["406819\/2022-0"],"award-info":[{"award-number":["406819\/2022-0"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)","award":["406819\/2022-0"],"award-info":[{"award-number":["406819\/2022-0"]}]},{"name":"Federal University of Par\u00e1 (UFPA)","award":["406819\/2022-0"],"award-info":[{"award-number":["406819\/2022-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Chronic treatment with dapsone (DDS) has been linked to adverse reactions involving all organ systems, such as dapsone hypersensitivity syndrome, methemoglobinemia and hemolytic anemia, besides neuroinflammation and neurodegeneration due to iron accumulation and oxidative stress. These effects probably occur due to the presence of its toxic metabolite DDS-NOH, which can generate reactive oxygen species (ROS) and iron overload. In this sense, antioxidant compounds with chelating properties, such as alpha-lipoic acid (ALA), may be an interesting adjuvant therapy strategy in treating or preventing these effects. Thus, the aim of this study was to evaluate the effects of ALA on oxidative and neuroinflammatory changes caused by DDS treatment in the prefrontal cortex and hippocampus of mice. Materials and Methods:Mus musculus male mice that were pre-treated with DDS (40 mg\/kg) and post-treated with ALA (25 mg\/kg) underwent analyses for oxidative stress, antioxidant capacity, cytokine expression and microglial\/astrocytic activity. Results: DDS did not activate macrophages\/microglia or astrocytes in the prefrontal cortex but induced their activation in the hippocampus. ALA stimulated a protective microglial profile and reduced astrocyte reactivity, especially in the hippocampus. DDS increased the pro-inflammatory cytokine IL-1\u03b2 and reduced brain-derived neurotrophic factor (BDNF), effects reversed by ALA. DDS also reduced antioxidant capacity (TEAC, GSH, SOD, CAT) and increased oxidative damage (lipid peroxidation, iron accumulation), while ALA restored antioxidant levels and reduced oxidative stress. Conclusions: ALA was able to reduce the effects of DDS, such as reducing microglial and astrocytic activation, as well as to decrease the levels of pro-inflammatory cytokines and increase BDNF, in addition to increasing antioxidant capacity and reducing oxidative damage caused by iron accumulation. Therefore, ALA is considered a useful and promising therapeutic alternative for the treatment of diseases related to oxidative stress and neuroinflammation.<\/jats:p>","DOI":"10.3390\/nu17050791","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T10:55:48Z","timestamp":1740480948000},"page":"791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Alpha-Lipoic Acid Reduces Neuroinflammation and Oxidative Stress Induced by Dapsone in an Animal Model"],"prefix":"10.3390","volume":"17","author":[{"given":"Bruno Alexandre Quadros","family":"Gomes","sequence":"first","affiliation":[{"name":"Postgraduate Program in Neuroscience and Cell Biology, Federal University of Par\u00e1\/UFPA, Rua Augusto Corr\u00eaa 01, Bairro Guam\u00e1, Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0927-9680","authenticated-orcid":false,"given":"Savio Monteiro dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Neuroscience and Cell Biology, Federal University of Par\u00e1\/UFPA, Rua Augusto Corr\u00eaa 01, Bairro Guam\u00e1, Bel\u00e9m 66075-110, PA, Brazil"},{"name":"Postgraduate Program in Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Par\u00e1\/UFPA, Rua Augusto Corr\u00eaa 01, Bairro Guam\u00e1, Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas da Silva","family":"Gato","sequence":"additional","affiliation":[{"name":"Laboratory Immunology, Microbiology and In Vitro Assays (LABEIM), Faculty of Pharmacy, Federal University of Par\u00e1\/UFPA, Bel\u00e9m 66075-110, PA, 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Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Davis","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmacology and Biochemistry, Faculty of Pharmacy, Federal University of Par\u00e1\/UFPA, Rua Augusto Corr\u00eaa 01, Bairro Guam\u00e1, Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8613-3223","authenticated-orcid":false,"given":"Kely Campos","family":"Navegantes-Lima","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Pharmaceutical Sciences, Faculty of Pharmacy, Federal University of Par\u00e1\/UFPA, Rua Augusto Corr\u00eaa 01, Bairro Guam\u00e1, Bel\u00e9m 66075-110, PA, Brazil"},{"name":"Laboratory Immunology, Microbiology and In Vitro Assays (LABEIM), Faculty of Pharmacy, Federal University of Par\u00e1\/UFPA, Bel\u00e9m 66075-110, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4872-234X","authenticated-orcid":false,"given":"Rommel Mario Rodriguez","family":"Burbano","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Ophir Loyola Hospital, Bel\u00e9m 66063-240, PA, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1039-2509","authenticated-orcid":false,"given":"Pedro Roosevelt Torres","family":"Romao","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Immunology, Federal University of Health Sciences of Porto Alegre, Porto Alegre 90050-170, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5510-6852","authenticated-orcid":false,"given":"Michael D.","family":"Coleman","sequence":"additional","affiliation":[{"name":"College of Health and Life Sciences, Aston University, Aston Triangle, 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