artículo
Trypanosoma cruzi: In vitro effect of aspirin with nifurtimox and benznidazole
Fecha
2010Registro en:
10.1016/j.exppara.2009.09.005
1090-2449
0014-4894
MEDLINE:19735656
WOS:000273884300004
Autor
Lopez Munoz, Rodrigo
Faundez, Mario
Klein, Sebastian
Escanilla, Sebastian
Torres, Gloria
Lee Liu, Dasfne
Ferreira, Jorge
Kemmerling, Ulrike
Orellana, Myriam
Morello, Antonio
Ferreira, Arturo
Maya, Juan D.
Institución
Resumen
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. (C) 2009 Elsevier Inc. All rights reserved.