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2025-01-01
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- PE - IAM - Artigos de Periódicos [1074]
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EFFECT OF L-LEUCINE METHYL ESTER ON GROWTH AND ULTRASTRUCTURE OF TRYPANOSOMA CRUZI
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Ultra-estrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Departamento de Biologia Celular e Ultra-estrutura. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Ultra-estrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Ultra-estrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil / Instituto de Biologia Molecular do Paraná. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Departamento de Biologia Celular e Ultra-estrutura. Recife, PE, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Ultra-estrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Ultra-estrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil / Instituto de Biologia Molecular do Paraná. Curitiba, PR, Brasil.
Abstract
l-Amino acid methyl esters, such as l-leucine methyl ester (Leu-OMe), have been identified as agents targeting the lysosomal
system of Leishmania amazonensis amastigotes, by a mechanism that involves ester hydrolysis by parasite enzymes located inside
megasomes.We have here analyzed the effect of Leu-OMe on all three evolutive forms of Trypanosoma cruzi, in a search for potential
targets of the compound in this protozoan. Treatment of epimastigote forms resulted in dose-dependent growth inhibition, with IC50/1
day = 0.55±0.21 mM. Incubation with 4–8 mM/1 day led to 100% cell death. Treatment of bloodstream trypomastigotes resulted
in cell lysis, with an IC50/1 day = 1.46±0.16 mM. Furthermore, infected macrophages treated with 0.125–1mM Leu-OMe showed
a dose- and time-dependent decrease in the percent of amastigote infection. Morphological changes in macrophages were observed
only at concentrations above 8 mM, at the third day of treatment. Analysis of treated parasites by transmission electron microscopy
demonstrated severe morphological alterations in cell shape, mitochondrion and nucleus, while kinetoplast and reservosomes (prelysosomal
compartments) appeared to be not affected. Lysis of bloodstream trypomastigotes and intracellular amastigotes indicated
that lysosomes of T. cruzi are the main target for the drug, since reservosomes occur only in epimastigote forms. The presence of
lysosomes in T. cruzi epimastigotes was demonstrated by using ultrastructural cytochemistry.
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