RESEARCH ARTICLE


Desynchronizing Plasmodium Cell Cycle Increases Chloroquine Protection at Suboptimal Doses



Piero Bagnaresi1, Regina P. Markus1, Carlos T. Hotta1, Tulio Pozzan 2, Célia R.S. Garcia *, 1
1 Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil
2 Department of Biomedical Sciences, Viale G. Colombo 3, 35121 Padua, Italy

Article Information


Identifiers and Pagination:

Year: 2008
Volume: 2
First Page: 55
Last Page: 58
Publisher ID: TOPARAJ-2-55
DOI: 10.2174/1874421400802010055

Article History:

Received Date: 10/4/2008
Revision Received Date: 28/5/2008
Acceptance Date: 3/1/2008
Electronic publication date: 30/6/2008
Collection year: 2008

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Creative Commons License
© 2008 Bagnaresiet al;

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Rua do Matão, travessa 14, n. 321. Cidade Universitária, São Paulo, Brazil 05508-900; Tel: +55(11)30917518; Fax: +55(11)30918095; E-mail: cgarcia@usp.br


Abstract

We have previously shown that in vivo and in vitro the hormone melatonin is responsible for the synchronous development of Plasmodia. Melatonin can also mobilize calcium from internal stores in these parasites and this response is abolished by luzindole, a melatonin antagonist. We here demonstrate that in vivo alteration of parasite synchronous development, using luzindole, partially improves survival of infected mice and dramatically increases the antimalarial activity of chloroquine. The data presented may lead to a conceptually new paradigm for malaria infection therapy and provide novel evidence suggesting that the malaria parasite uses the cell cycle synchrony as one of the strategies to evade the host immune system.

Keywords: Malaria, Plasmodium, Rhythm, Chloroquine.