Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/37809
Title: Anti-proliferative synergy of lysophospholipid analogues and ketoconazole against Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae): cellular and ultrastructural analysis
Authors: Santa-Rita, Ricardo M.
Lira, Renee
Barbosa, Helene Santos
Urbina, Julio A.
Castro, Solange L. de
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departmento de Ultra-estrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil.
Instituto Venezolano de Investigaciones Científicas. Centro de Biofísica y Bioquímica. Laboratório de Química Biológica. Caracas, Venezuela.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departmento de Ultra-estrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil.
Instituto Venezolano de Investigaciones Científicas. Centro de Biofísica y Bioquímica. Laboratório de Química Biológica. Caracas, Venezuela.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departmento de Ultra-estrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil.
Abstract: Objectives: Investigation of the antiproliferative synergy of the lysophospholipid analogues (LPAs) edelfosine, ilmofosine and miltefosine with the ergosterol biosynthesis inhibitor ketoconazole against Trypanosoma cruzi. Methods: The effect of LPAs, ketoconazole and their combination was evaluated against epimastigotes and intracellular amastigotes by the parameter IC50 leading to construction of isobolograms, for determination of a synergic effect. For epimastigotes, ultrastructural damage induced by these treatments was evaluated by transmission and scanning electron microscopy. Results: Synergy was confirmed against both epimastigotes and amastigotes of the parasite. Edelfosine or ketoconazole alone induced morphological alterations in the plasma membrane and reservosomes of the parasites, while in combination, they also led to severe mitochondrial damage, formation of autophagic structures and multinucleation. Scanning electron microscopy confirmed the effect at the plasma membrane and also revealed alterations in the shape of the parasites. Conclusions: Our results describe the synergic anti-proliferative effect of LPAs and ketoconazole against epimastigotes and intracellular amastigotes and suggest that in epimastigotes, plasma membrane, reservosomes and mitochondria are targets of these drugs, possibly by interference with lipid metabolism.
Keywords: Trypanosoma cruzi
Chemotherapy
Edelfosine
Ilmofosine
Miltefosine
Sinergy
keywords: Trypanosoma cruzi
Quimioterapia
Sinergia
Issue Date: 2005
Publisher: Oxford University Press
Citation: SANTA-RITA, Ricardo M. et al. Anti-proliferative synergy of lysophospholipid analogues and ketoconazole against Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae): cellular and ultrastructural analysis. Journal of Antimicrobial Chemotherapy, v. 55, p. 780-784, 2005.
DOI: 10.1093/jac/dki087
ISSN: 0305-7453
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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