Artículo de revista
Trypanosoma cruzi: In vitro effect of aspirin with nifurtimox and benznidazole
Fecha
2010Registro en:
Experimental Parasitology 124 (2010) 167–171
doi:10.1016/j.exppara.2009.09.005
Autor
López Muñoz, Rodrigo
Faúndez, Mario
Klein, Sebastián
Escanilla, Sebastián
Torres, Gloria
Lee-Liu, Dasfne
Ferrada Parker, Jorge
Kemmerling Weis, Ulrike
Orellana Bown, Myriam
Morello Casté, Antonio
Ferreira, Arturo
Maya Arango, Juan
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 b and
PGE2 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 PGE2 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.