| Author | Santa-Rita, Ricardo M. | |
| Author | Lira, Renee | |
| Author | Barbosa, Helene Santos | |
| Author | Urbina, Julio A. | |
| Author | Castro, Solange L. de | |
| Access date | 2019-12-10T17:46:02Z | |
| Available date | 2019-12-10T17:46:02Z | |
| Document date | 2005 | |
| 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. | pt_BR |
| ISSN | 0305-7453 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/37809 | |
| Language | eng | pt_BR |
| Publisher | Oxford University Press | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Quimioterapia | pt_BR |
| Subject in Portuguese | Sinergia | pt_BR |
| Title | Anti-proliferative synergy of lysophospholipid analogues and ketoconazole against Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae): cellular and ultrastructural analysis | pt_BR |
| Type | Article | |
| DOI | 10.1093/jac/dki087 | |
| 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. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departmento de Ultra-estrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Instituto Venezolano de Investigaciones Científicas. Centro de Biofísica y Bioquímica. Laboratório de Química Biológica. Caracas, Venezuela. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departmento de Ultra-estrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Instituto Venezolano de Investigaciones Científicas. Centro de Biofísica y Bioquímica. Laboratório de Química Biológica. Caracas, Venezuela. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departmento de Ultra-estrutura e Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Trypanosoma cruzi | pt_BR |
| Subject | Chemotherapy | pt_BR |
| Subject | Edelfosine | pt_BR |
| Subject | Ilmofosine | pt_BR |
| Subject | Miltefosine | pt_BR |
| Subject | Sinergy | pt_BR |
| e-ISSN | 1460-2091 | |
