Alpha-Lipoic Acid and Its Enantiomers Prevent Methemoglobin Formation and DNA Damage Induced by Dapsone Hydroxylamine: Molecular Mechanism and Antioxidant Action

Abstract

Dapsone (DDS) therapy can frequently lead to hematological side effects, such as methemoglobinemia and DNA damage. In this study, we aim to evaluate the protective effect of racemic alpha lipoic acid (ALA) and its enantiomers on methemoglobin induction. The pre- and post-treatment of erythrocytes with ALA, ALA isomers, or MB (methylene blue), and treatment with DDS-NOH (apsone hydroxylamine) was performed to assess the protective and inhibiting effect on methemoglobin (MetHb) formation. Methemoglobin percentage and DNA damage caused by dapsone and its metabolites were also determined by the comet assay. We also evaluated oxidative parameters such as SOD, GSH, TEAC (Trolox equivalent antioxidant capacity) and MDA (malondialdehyde). In pretreatment, ALA showed the best protector effect in 2.5 µg/mL of DDS-NOH. ALA (1000 µM) was able to inhibit the induced MetHb formation even at the highest concentrations of DDS-NOH. All ALA tested concentrations (100 and 1000 µM) were able to inhibit ROS and CAT activity, and induced increases in GSH production. ALA also showed an effect on DNA damage induced by DDS-NOH (2.5 µg/mL). Both isomers were able to inhibit MetHb formation and the S-ALA was able to elevate GSH levels by stimulating the production of this antioxidant. In post-treatment with the R-ALA, this enantiomer inhibited MetHb formation and increased GSH levels. The pretreatment with R-ALA or S-ALA prevented the increase in SOD and decrease in TEAC, while R-ALA decreased the levels of MDA; and this pretreatment with R-ALA or S-ALA showed the effect of ALA enantiomers on DNA damage. These data show that ALA can be used in future therapies in patients who use dapsone chronically, including leprosy patients.

Publication DOI: https://doi.org/10.3390/ijms24010057
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Additional Information: © 2022 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: alpha lipoic acid,Thioctic Acid - pharmacology,DNA damage,Dapsone - pharmacology,dapsone,Superoxide Dismutase,DNA Damage,Antioxidants - pharmacology,Methemoglobin - metabolism
Publication ISSN: 1422-0067
Last Modified: 16 May 2024 07:17
Date Deposited: 23 Jan 2023 14:05
Full Text Link:
Related URLs: https://www.mdp ... 22-0067/24/1/57 (Publisher URL)
PURE Output Type: Article
Published Date: 2022-12-21
Published Online Date: 2022-12-21
Accepted Date: 2022-10-23
Submitted Date: 2022-09-15
Authors: Espíndola, Kaio Murilo Monteiro
Varela, Everton Luiz Pompeu
de Albuquerque, Rosyana de Fátima Vieira
Figueiredo, Rosiane Araújo
Dos Santos, Sávio Monteiro
Malcher, Nívea Silva
da S Seabra, Pamela Suelen
Fonseca, Andréia do Nascimento
de Azevedo Sousa, Karla Marcely
de Oliveira, Susan Beatriz Batista
Carneiro, Agnaldo da Silva
Coleman, Michael D (ORCID Profile 0000-0002-5510-6852)
Monteiro, Marta Chagas

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