Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis.

Resumo
Aims: Treatment for visceral leishmaniasis (VL) is hampered by the toxicity and/or high cost of drugs, as well as by emergence of parasite resistance. Therefore, there is an urgent need for new antileishmanial agents. Methods and Results: In this study, the antileishmanial activity of a diprenylated flavonoid called 5,7,3,4’-tetrahydroxy-6,8-diprenylisoflavone (CMt) was tested against Leishmania infantum and L amazonensis species. Results showed that CMt presented selectivity index (SI) of 70.0 and 165.0 against L infantum and L amazonensis promastigotes, respectively, and of 181.9 and 397.8 against respective axenic amastigotes. Amphotericin B (AmpB) showed lower SI values of 9.1 and 11.1 against L infantum and L amazonensis promastigotes, respectively, and of 12.5 and 14.3 against amastigotes, respectively. CMt was effective in the treatment of infected macrophages and caused alterations in the parasite mitochondria. L infantum-infected mice treated with miltefosine, CMt alone or incorporated in polymeric micelles (CMt/Mic) presented significant reductions in the parasite load in distinct organs, when compared to the control groups. An antileishmanial Th1-type cellular and humoral immune response were developed one and 15 days after treatment, with CMt/Mic-treated mice presenting a better protective response. Conclusion: Our data suggest that CMt/Mic could be evaluated as a chemotherapeutic agent against VL.
Descrição
Palavras-chave
Delivery systems, Flavonoids, Immune response, Miltefosine, Treatment
Citação
PEREIRA, I. A. G. et al. Parasitological and immunological evaluation of a novel chemotherapeutic agent against visceral leishmaniasis. Parasite Immunology, v. 42, n. 12, artigo e12784, dez. 2020. Disponível em: <https://onlinelibrary.wiley.com/doi/abs/10.1111/pim.12784>. Acesso em: 10 jun. 2021.