Trypanosoma cruzi: In vitro effect of aspirin with nifurtimox and benznidazole
link https://doi.org/10.1016/j.exppara.2009.09.005account_box Lopez Munoz, Rodrigoaccount_box Faundez, Marioaccount_box Klein, Sebastianaccount_box Escanilla, Sebastianaccount_box Torres, Gloriaaccount_box Lee Liu, Dasfneaccount_box Ferreira, Jorgeaccount_box Kemmerling, Ulrikeaccount_box Orellana, Myriamaccount_box Morello, Antonioaccount_box Ferreira, Arturoaccount_box Maya, Juan D.
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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.
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| 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. |
| Título | Trypanosoma cruzi: In vitro effect of aspirin with nifurtimox and benznidazole |
| Revista | EXPERIMENTAL PARASITOLOGY |
| ISSN | 0014-4894 |
| ISSN electrónico | 1090-2449 |
| Volumen | 124 |
| Número de publicación | 2 |
| Página inicio | 167 |
| Página final | 171 |
| Fecha de publicación | 2010 |
| 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. |
| Derechos | acceso restringido |
| DOI | 10.1016/j.exppara.2009.09.005 |
| Editorial | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| Enlace | |
| Id de publicación en Pubmed | MEDLINE:19735656 |
| Id de publicación en WoS | WOS:000273884300004 |
| Paginación | 5 páginas |
| Palabra clave | Trypanosoma cruzi Aspirin Nifurtimox Benznidazole Synergism GROWTH-FACTOR-BETA APOPTOTIC CELLS ACUTE-PHASE INFECTION MACROPHAGES PROSTAGLANDIN PROLIFERATION METABOLISM SYNERGISM TOXICITY |
| Tema ODS | 03 Good Health and Well-being |
| Tema ODS español | 03 Salud y bienestar |
| Tipo de documento | artículo |