Dapsone (DDS), a drug used in leprosy multidrug therapy, can cause many adverse reactions and intoxications, inducing the generation of reactive oxygen species (ROS) and imbalance in the redox state, increase methemoglobin (MetHb) formation, hemolysis and release of heme and iron free, which may interfere with redox homeostasis in more vulnerable regions, such as prefrontal cortex (PFC), causing neurotoxicity and even neuroinflammation. In this sense, antioxidant compounds with chelating properties such as α-lipoic acid (ALA) may play a key role in combating or preventing these alterations. Thus, this work aims to evaluate the effect of DDS on MetHb formation, peripheral oxidative stress, and oxidative changes and neuroinflammation in PFC, as well as, effects of ALA. For this, was induced MetHb formation in Swiss mice with DDS 40mg/kg ip for 5 days. Two hours after DDS administration, ALA was given at two concentrations (12.5 and 25 mg/kg). Besides MetHb percentage, total equivalent antioxidant capacity (TEAC), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) thiobarbituric acid reactive substances (TBARS), and iron concentrations in blood and PFC were evaluated, as well as, IL-1β, IL-17, and IL-4 cytokine concentrations, and de F4/80+, GFAP, and BDNF expression in PFC. Our results show that DDS induces the MetHb formation in red blood cells of mice, however, ALA was able to prevent or reverse the oxidation of hemoglobin induced by DDS at two used concentrationns. DDS reduced antioxidant capacity (TEAC) in plasma and red blood cells; decreased erythrocyte GSH, CAT, and SOD; and increased TBARS and plasma iron; however, ALA at two concentrations increased or reestablished TEAC in plasma and red blood cells at baseline levels. In addition to increasing or reestablishing GSH levels, SOD, and CAT in red blood cells, and decreased TBARS and iron levels, mainly in euthanized animals 4h after treatment. Curiously ALA 50mg/kg increased plasma iron concentrations. The treatment with DDS 40mg/kg also reduced TEAC, GSH, SOD e CAT in the PFC of the mice and increased TBARS and iron, characterizing oxidative stress, mainly in euthanized animals in 24h after treatment. Treatment with ALA increased or restored TEAC and GSH; and increased SOD and CAT in 12,5mg/kg concentration in euthanized animals 4h after treatment, as well as reducing TBARS levels and decreasing or preventing iron overload, mainly in euthanized animals 24h after treatment. DDS also promoting microglial and astrocyte activation in PFC, through F4/80+ e GFAP expression., with increased IL-1β and IL-4 production, and BDNF reduction, on the other hand, ALA 25mg/kg reduced GFAP and IL-1β expression, besides increased BDNF, suggesting that DDS also can cause neuroinflammation, and ALA presents antioxidant and anti-inflammatory properties against toxicity caused by DDS. These results suggest that ALA is promising and plays an important role in the prevention and/or formation of MetHb, reestablishment of redox balance and iron concentrations in both blood and PFC. Thus, ALA may be a usefull adjuvant therapy in DDS-induced toxicity, with lower toxicity and increasing adherence to treatment of leprosy patients.
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