TY - JOUR
T1 - Trypanosoma cruzi
T2 - In vitro effect of aspirin with nifurtimox and benznidazole
AU - López-Muñoz, Rodrigo
AU - Faúndez, Mario
AU - Klein, Sebastián
AU - Escanilla, Sebastián
AU - Torres, Gloria
AU - Lee-Liu, Dasfne
AU - Ferreira, Jorge
AU - Kemmerling, Ulrike
AU - Orellana, Myriam
AU - Morello, Antonio
AU - Ferreira, Arturo
AU - Maya, Juan D.
N1 - Funding Information:
We thank Dr. Norbel Galanti (Cellular and Molecular Biology Program, ICBM, Faculty of Medicine, University of Chile) for critical review of this paper. FONDECYT 1090078, PBCT ANILLO ACT 29 and REDES-07, Chilean grants supported this research.
PY - 2010/2
Y1 - 2010/2
N2 - 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 β 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{radical dot} 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.
AB - 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 β 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{radical dot} 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.
KW - Aspirin
KW - Benznidazole
KW - Nifurtimox
KW - Synergism
KW - Trypanosoma cruzi
UR - http://www.scopus.com/inward/record.url?scp=73649109547&partnerID=8YFLogxK
U2 - 10.1016/j.exppara.2009.09.005
DO - 10.1016/j.exppara.2009.09.005
M3 - Article
C2 - 19735656
AN - SCOPUS:73649109547
SN - 0014-4894
VL - 124
SP - 167
EP - 171
JO - Experimental Parasitology
JF - Experimental Parasitology
IS - 2
ER -
