Dados do Trabalho

Título

MSS: a promising repositioning in leishmaniasis treatment

Introdução

Leishmaniasis is a neglected tropical disease caused by different species of Leishmania. The treatment of leishmaniasis involves a limited drug arsenal and is associated with problems such as therapeutic failure, high toxicity, high costs and the emergence of resistant. Among the search for new alternatives to combat these diseases, drug repositioning stands out. In this scenario, we highlight MSS, a drug currently used in the clinic for the treatment of a nonparasitic disease.

Objetivo (s)

This study evaluated MSS in vitro and in vivo effects against Leishmania and its possible mechanism of action.

Material e Métodos

Promastigotes of L. infantum and L. amazonensis were treated with different concentrations of MSS (18,75μM–1200μM) for 24 and 72 h respectively and demonstrated an inhibition of cellular viability in a concentration-dependent manner. To investigate a possible mechanism of action, promastigotes treated with MSS showed a concentration-dependent increase in ROS levels in both species. Concerning the murine model of visceral leishmaniasis, in the in vivo study, two types of treatments were used , short-term and long-term. BALB/c mice were infected with L. infantum promastigotes for 7 days and treated with 1,5, 3 or 6mg/kg/day of MSS, 100mg/kg/day of glucantime or the vehicle and the animals were euthanized right after the treatment (short) or 18 days after (long).

Resultados e Conclusão

The IC50 value of L. infantum promastigotes was 821.4μM (24h) and 273.5μM (72h), and in L. amazonensis promastigotes was 336.1μM (24h) and 428.8μM (72h). Preincubation with antioxidant molecules (300μM) were not capable of protecting cells from the inhibition promoted by MSS , suggesting that ROS production is a consequence and not the cause of cell death. Against the intracellular amastigote, MSS (4–280μM) demonstrated an inhibition of the infection index in a concentration-dependent manner after 72 hours of treatment in both species, and proved to be not toxic in the macrophage toxicity assay. The IC50 value of intracellular amastigotes was 5.49μM and 3.31μM for L. infantum and L. amazonensis respectively. In vivo, MSS was able to decrease the parasite load in the liver and spleen of infected mice compared to the control and glucantime groups. Serological toxicology markers were evaluated, and no significant changes were observed, suggesting the absence of liver and kidney toxicity. Taken together, these results suggest that MSS is a good possibility for leishmaniasis chemotherapy.

Palavras-chave

Repositioning, leishmaniasis