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.

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.

Central America is home to one of the most abundant herpetofauna in the Americas, occupying only 7% of the continent’s total area. Vipers and lizards are among the most relevant venomous animals in medical practice due to the consequences of envenomation from the bite of these animals. A great diversity of biomolecules with immense therapeutic and biotechnological value is contained in their venom. This paper describes the prominent leading representatives of the family Viperidae, emphasizing their morphology, distribution, habitat, feeding, and venom composition, as well as the biotechnological application of some isolated components from the venom of the animals from these families, focusing on molecules with potential anti-thrombotic action. We present the leading protein families that interfere with blood clotting, platelet activity, or the endothelium pro-thrombotic profile. In conclusion, Central America is an endemic region of venomous animals that can provide many molecules for biotechnological applications.