Avaliação da atividade antileishmanial da Ivermectina no tratamento da Leishmaniose Tegumentar

Abstract

Tegumentary leishmaniasis (TL) is a neglected parasitic disease complex that affects millions of people worldwide, mainly in tropical and subtropical regions. Treatment is associated with toxicity, parasite resistance and high cost; making urgent the development of more effective and safer therapies. Ivermectin (IVE) is an antiparasitic agent with an established safety profile in humans. The drug has immunomodulatory properties that may be advantageous in the context of leishmaniasis, since it is capable of stimulating the development of a Th1-type immune response. In this context, in the present study, IVE was used in free form or incorporated into a polymeric micelle system based on Poloxamer P407 (IVE/M), and its antileishmanial activity was in vivo evaluated in BALB/c mice infected with Leishmania (L.) amazonensis, an important parasite species that causes TL in the Americas. Amphotericin B (AmpB) was used as control. Parasitological and immunological evaluations were performed one and 30 days after treatment. Results showed that IVE and, mainly, IVE/M reduced the mean diameter of lesions caused by L. amazonensis and the parasite load in the infected tissue, liver, spleen and draining lymph nodes, when compared to the control groups. These animals developed a Th1-type response specific to the parasites, with high levels of IFN-gamma, IL-12, GM-CSF and nitrite, in addition to IgG2a antibodies, associated with low levels of IL-4, IL-10 and IgG1 antibodies. These animals presented also low organ toxicity by the evaluation of hepatic and renal damage markers, when compared to the other groups. IVE/M was more effective than the free IVE in the therapeutic response against infection in the animals, in both periods of time. In conclusion, the micellar composition could be considered a therapeutic candidate against TL.