Skip Navigation


JAC Advance Access originally published online on March 24, 2005
Journal of Antimicrobial Chemotherapy 2005 55(5):780-784; doi:10.1093/jac/dki087
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
55/5/780    most recent
dki087v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (17)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Santa-Rita, R. M.
Right arrow Articles by de Castro, S. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Santa-Rita, R. M.
Right arrow Articles by de Castro, S. L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions{at}oupjournals.org

Anti-proliferative synergy of lysophospholipid analogues and ketoconazole against Trypanosoma cruzi (Kinetoplastida: Trypanosomatidae): cellular and ultrastructural analysis

Ricardo M. Santa-Rita1, Renee Lira2, Helene Santos Barbosa1, Julio A. Urbina2 and Solange L. de Castro1,*

1 Departmento de Ultra-estrutura e Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, CP 926, 21045-900, Rio de Janeiro, Brazil; 2 Laboratorio de Química Biológica, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Apartado Postal 21.627, Caracas 1020A, Venezuela

* Corresponding author. Tel: +55-21-25984330; Fax: +55-21-2604434; Email: solange{at}ioc.fiocruz.br

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: T. cruzi , chemotherapy , edelfosine , ilmofosine , miltefosine , synergy


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Evid Based Complement Alternat MedHome page
K. Salomao, E. M. de Souza, A. Henriques-Pons, H. S. Barbosa, and S. L. de Castro
Brazilian Green Propolis: Effects In Vitro and In Vivo on Trypanosoma cruzi
Evid. Based Complement. Altern. Med., March 11, 2009; (2009) nep014v2.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. E. Alvarez, G. Kosec, C. Sant'Anna, V. Turk, J. J. Cazzulo, and B. Turk
Autophagy Is Involved in Nutritional Stress Response and Differentiation in Trypanosoma cruzi
J. Biol. Chem., February 8, 2008; 283(6): 3454 - 3464.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
N. L. Uzcategui, D. Carmona-Gutierrez, V. Denninger, C. Schoenfeld, F. Lang, K. Figarella, and M. Duszenko
Antiproliferative Effect of Dihydroxyacetone on Trypanosoma brucei Bloodstream Forms: Cell Cycle Progression, Subcellular Alterations, and Cell Death
Antimicrob. Agents Chemother., November 1, 2007; 51(11): 3960 - 3968.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
J. R. Luque-Ortega and L. Rivas
Miltefosine (Hexadecylphosphocholine) Inhibits Cytochrome c Oxidase in Leishmania donovani Promastigotes
Antimicrob. Agents Chemother., April 1, 2007; 51(4): 1327 - 1332.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.