In vitro and in vivo activity of voriconazole and benznidazole combination on trypanosoma cruzi infection models
| Autor: | Mackenzie A. Eagleson, María Elisa Solana, Rodrigo López-Muñoz, Facundo Garcia-Bournissen, Jaime Altcheh, Julián Ernesto Nicolás Gulin |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Chagas disease CIENCIAS MÉDICAS Y DE LA SALUD Combination therapy Veterinary (miscellaneous) Trypanosoma cruzi 030231 tropical medicine Ciencias de la Salud Parasitemia Pharmacology In Vitro Techniques Trypcmosoma cruzi Pediatrics 03 medical and health sciences Mice 0302 clinical medicine In vitro In vivo parasitic diseases Chlorocebus aethiops medicine Animals Chagas Disease Drug combination IC50 Vero Cells Voriconazole biology Chemistry Drug Synergism 030108 mycology & parasitology medicine.disease biology.organism_classification Trypanocidal Agents Enfermedades Infecciosas Infectious Diseases Benznidazole Nitroimidazoles Insect Science Parasitology medicine.drug |
| Zdroj: | Paediatrics Publications |
| ISSN: | 1873-6254 |
| Popis: | Combination therapy has been proposed as an ideal strategy to reduce drug toxicity and improve treatment efficacy in Chagas disease. Previously, we demonstrated potent in vivo anti-Trypanosoma cruzi activity of voriconazole. In this work, we aimed to study the synergistic effect of voriconazole (VCZ) and benznidazole (BZ) both in vitro and in vivo models of T. cruzi infection using the Tulahuen strain. Combining VCZ and BZ at fixed concentrations, the inhibitory concentration 50% (IC50) on amastigotes was lower than the obtained IC50 for BZ alone and the Fractional Inhibitory Concentration Index (∑FIC) suggested an in vitro additive effect on T. cruzi amastigotes inhibition at concentrations devoid of cytotoxic effects. Treatment response in the in vivo model was evaluated by comparing behavior and physical aspects, parasitemia and mortality of mice infected with Tulahuen strain. VCZ and BZ treatments alone or in combination were well tolerated. All treated animals displayed significantly lower mean peak parasitemia and mortality compared to infected non-treated controls (p< 0.05). However, VCZ + BZ combination elicited no additional benefits over BZ monotherapy. VCZ efficacy was not enhanced by combination therapy with BZ at the doses studied, requiring further and astringent non-clinical studies to establish the VCZ efficacy and eventually moving forward to clinical trials. Fil: Gulin, Julián Ernesto Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Eagleson, Mackenzie Anne. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Harvard University; Estados Unidos Fil: López Muñoz, Rodrigo A.. Universidad Austral de Chile; Chile Fil: Solana, María Elisa. Universidad Nacional de Luján; Argentina. Universidad de Buenos Aires; Argentina Fil: Altcheh, Jaime Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: García Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Western University; Canadá |
| Databáze: | OpenAIRE |
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