Alpha-Lipoic Acid Reduces Neuroinflammation and Oxidative Stress Induced by Dapsone in an Animal Model

Abstract

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-1β 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.

Publication DOI: https://doi.org/10.3390/nu17050791
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
Funding Information: This research was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; Funding number: 406819/2022-0), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Federal University of Pará (UFPA).
Additional Information: Copyright © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Uncontrolled Keywords: dapsone,neuroinflammation,alpha lipoic acid
Publication ISSN: 2072-6643
Last Modified: 26 Mar 2025 17:01
Date Deposited: 07 Mar 2025 15:54
Full Text Link:
Related URLs: https://www.mdp ... 2-6643/17/5/791 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2025-03
Published Online Date: 2025-02-25
Accepted Date: 2025-02-19
Authors: Gomes, Bruno Alexandre Quadros
Santos, Savio Monteiro dos
Gato, Lucas da Silva
Espíndola, Kaio Murilo Monteiro
Silva, Rana Karen Mesquita da
Davis, Kelly
Navegantes-Lima, Kely Campos
Burbano, Rommel Mario Rodriguez
Romao, Pedro Roosevelt Torres
Coleman, Michael D. (ORCID Profile 0000-0002-5510-6852)
Monteiro, Marta Chagas

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