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Evaluation of the activity of macrophage FABP4 inhibitors in Leishmania infections

Grant number: 15/26408-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2016
Effective date (End): January 31, 2017
Field of knowledge:Biological Sciences - Parasitology
Principal Investigator:Danilo Ciccone Miguel
Grantee:Vivian Midori Maruyama
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:14/21129-4 - The role of fatty acid-binding proteins in the macrophage infection by Leishmania: a potential target for new drugs against leishmaniasis, AP.JP

Abstract

The fatty acid-binding protein type 4 (FABP4) is present in the cytosol of macrophages and adipocytes and participate in the fatty acids traffic to different cellular compartments. The investigation of its role in the course of Leishmania infection is the main objective of the project 14 / 21129-4, supported by FAPESP. Initially, the toxicity profile of two specific inhibitors of FABP4 activity will be determined using: i) bone marrow derived macrophages from BALB/c mice; ii) promastigote cultures for three important species of Leishmania in Brazil: Leishmania (Leishmania) infantum chagasi, L. (L.) amazonensis and L. (V.) braziliensis. Optimal ranges of concentrations for each of these inhibitors will be calculated for further evaluation of the activity of the inhibitors in Leishmania-infected macrophages after 24, 48 and 72 hours. Results will be presented as inhibitory concentrations for 50 and 90% cell viability (CC50%; EC50%; EC90%), and infectivity index (total percentage of macrophage infection and the number of amastigotes per macrophage). This initial work will expand our comprehension on the role of FABP4 in the infective process of different Leishmania species when residing in host cells.