| Literature DB >> 19735656 |
Rodrigo López-Muñoz1, Mario Faúndez, Sebastián Klein, Sebastián Escanilla, Gloria Torres, Dasfne Lee-Liu, Jorge Ferreira, Ulrike Kemmerling, Myriam Orellana, Antonio Morello, Arturo Ferreira, Juan D Maya.
Abstract
Nifurtimox and benznidazole are the only active drugs against Trypanosoma cruzi; however, they have limited efficacy and severe side effects. During primoinfection, T. cruzi infected macrophages mount an antiparasitic response, which the parasite evades through an increase of tumor growth factor beta and PGE(2) activation as well as decreased iNOS activity. Thus, prostaglandin synthesis inhibition with aspirin might increase macrophage antiparasitic activity and increase nifurtimox and benznidazole effect. Aspirin alone demonstrated a low effect upon macrophage antiparasitic activity. However, isobolographic analysis of the combined effects of aspirin, nifurtimox and benznidazole indicated a synergistic effect on T. cruzi infection of RAW cells, with combinatory indexes of 0.71 and 0.61, respectively. The observed effect of aspirin upon T. cruzi infection was not related with the PGE(2) synthesis inhibition. Nevertheless, NO() levels were restored by aspirin in T. cruzi-infected RAW cells, contributing to macrophage antiparasitic activity improvement. Thus, the synergy of aspirin with nifurtimox and benznidazole is due to the capability of aspirin to increase antiparasitic activity of macrophages. Copyright 2009 Elsevier Inc. All rights reserved.Entities:
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Year: 2009 PMID： 19735656 DOI： 10.1016/j.exppara.2009.09.005
Source DB: PubMed Journal: Exp Parasitol ISSN： 0014-4894 Impact factor: 2.011