Alpha-Lipoic Acid Reduces Methemoglobin and Oxidative Imbalance in the Blood and Liver Induced by Dapsone in Mice: Molecular Mechanism of Antioxidant Action

TL;DR

Alpha-lipoic acid helps reduce oxidative stress and harmful effects caused by dapsone in mice, offering a potential treatment strategy.

Contribution

The study reveals the molecular mechanism by which alpha-lipoic acid counteracts dapsone-induced oxidative damage.

Findings

Alpha-lipoic acid reduced methemoglobin and oxidative stress in blood and liver of dapsone-intoxicated mice.

Molecular docking suggests alpha-lipoic acid inhibits the toxic metabolite DDS-NOH.

ALA restored redox status and reduced iron accumulation and hepatic enzyme production.

Abstract

Dapsone (DDS) is a sulfone clinically used in the treatment
of
dermatological disorders, such as dermatitis herpetiformis and psoriasis,
besides Toxoplasma gondii, Pneumocystis carinii, and Mycobacterium
leprae infections. However, the chronic use of DDS
can lead to adverse effects involving all organ systems, such as dapsone
hypersensitivity syndrome, methemoglobinemia, hemolytic anemia, and
liver injury. These effects probably occur due to the presence of
its toxic metabolite DDS-NOH, which can generate reactive oxygen species
(ROS), and iron overload, causing oxidative stress. 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 oxidative stress and adverse reactions related to DDS.
This study showed that DDS 40 mg/kg increased the methemoglobin and
induced oxidative stress in the erythrocytes and liver of mice. However,
post-treatment with ALA 12.5 mg/kg was able to restore redox status
and hepatic biomarkers in DDS-intoxicated animals. Thus, inhibiting
the formation of methemoglobin and lipid peroxidation in the blood,
as well as reducing iron accumulation and production of hepatic enzymes
stimulated by DDS metabolism. In addition, the molecular docking shows
that ALA in its oxidized form can inhibit DDS-NOH. These findings
highlight the potential of ALA and its thiol derivatives as antioxidants
in counteracting the harmful effects of DDS metabolites. However,
further investigations are necessary to understand the therapeutic
potential and antioxidant mechanisms of ALA and its derivatives for
the development of new strategies to prevent or alleviate oxidative
damage associated with DDS treatment.

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