Dados do Trabalho

Título

2'-hydroxyflavanone activity against wild-type and antimony-resistant Leishmania infantum

Introdução

Leishmaniasis are neglected tropical diseases with a high annual incidence and a wide spectrum of clinical manifestations. Visceral leishmaniasis (VL) is the most severe form, in which untreated or late diagnosed cases can lead to death. Leishmaniasis therapeutic arsenal is still ineffective, high-cost, highly toxic, and have been reported cases of resistance in recent years. Among the search for new alternatives for leishmaniasis treatment, many studies have demonstrated the leishmanicidal effect of natural products, highlighting flavonoids, a class of secondary metabolites of plants with antioxidant and anti-inflammatory properties already described. Previous studies demonstrated in vitro and in vivo effects of 2'-hidroxiflavanone (2HF), a flavanone already known for its activity in tumor cells, against wild type and antimony-resistant L. amazonensis.

Objetivo (s)

Considering VL importance and 2HF previous results in Cutaneous Leishmaniasis, the aim of this study is to evaluate 2HF in vitro and in vivo activity against wild type and antimony-resistant L. infantum.

Material e Métodos

Wild-type and antimony-resistant promastigotes of L. infantum were incubated with increasing concentrations of 2HF (0 – 96 µM) for 72h. Cell viability was obtained by resazurin. In antiamastigote assay, Balb/c peritoneal macrophages were infected with wild type L. infantum promastigotes and treated with increasing concentrations of 2HF (0 - 96 µM). In order to evaluate 2HF in vivo effect in a murine model of visceral leishmaniasis, Balb/c mice were infected intraperitoneally with L. infantum promastigotes. After 21 days of infection, mice were treated orally with 2HF (25, 50 or 100 mg/Kg/day) for 5 days with a 12h/12h scheme and then euthanized. Livers were collected and parasite load analysis was performed by limiting dilution assay (LDA).

Resultados e Conclusão

2HF inhibited wild type and antimony-resistant promastigotes of L. infantum in a concentration-dependent manner, with IC50 values of 46.4 μM and 38, respectively. 2HF demonstrated an IC50 of 3.2 μM for intracellular amastigotes, reducing significantly the number of amastigotes and infected macrophages. In an in vivo model of VL, 2HF reduced the parasite load in the liver in a dose-dependent manner, reaching a 99% inhibition at 100 mg/kg/day. Taken together, these results indicate 2HF promising effects against L. infantum, pointing the flavonoid as a possible future candidate for visceral leishmaniasis treatment.

Palavras-chave

Leishmaniasis, Flavonoids, Chemoterapy, Resistance