AVALIAÇÃO DA ATIVIDADE ANTILEISHMANIA DA PLA2 Lys49 MjTX-I, ISOLADA DA PEÇONHA DE Bothrops moojeni

Abstract

Leishmaniasis is a disease caused by protozoa of the genus Leishmania. The currently available treatment presents high toxicity, high cost, parasite resistance and difficulties in cure. In this sense, snake venoms are a promising source of study, since they have a series of bioactive compounds with therapeutic potential, among these, phospholipases A2 (PLA2) stand out. Thus, the objective of the present study was to evaluate the effect of PLA2 MjTX -I, isolated from Bothrops moojeni venom on the growth and viability of promastigote forms of Leishmania Leishmania amazonensis. In addition, were evaluated, changes in the parasite's ultrastructure and action of the toxin in the process of infectivity in macrophages. MjTX-I showed activity against the promastigote forms of the parasite at 24 and 72 hours, with an IC50= 36.54 ug / mL 72 hours after treatment. Furthermore, the results of the growth curve demonstrate a total inhibition of parasite proliferation at a concentration of 40μg/ mL of the toxin after 72 hours of treatment. Ultrastructural studies by scanning electron microscopy in promastigotes treated with MjTX-I revealed the presence of a double flagellum and rounding of the parasite tip. It was also observed that the toxin increased the production of ROS and decreased the membrane potential in the assay (10 and 40 μg / mL) using the rhodamine 123 probe. MjTX-I interfered with the invasion capacity of the pre-treated promastigotes (10 and 40 μg / mL), decreasing the number of infected cells and the number of parasites per infected cell. Finally, the treatment of infected macrophages reduced the proliferation of parasites (10 μg / mL) at 72 hours. Our results suggest that PLA2 MjTX-I is an important tool for the discovery of new targets in the parasite that can be exploited for the development of new drugs for the treatment of leishmaniasis.