info:eu-repo/semantics/article
In vitro and in vivo activity of voriconazole and benznidazole combination on trypanosoma cruzi infection models
Fecha
2020-11Registro en:
Gulin, Julián Ernesto Nicolás; Eagleson, Mackenzie Anne; López Muñoz, Rodrigo A.; Solana, María Elisa; Altcheh, Jaime Marcelo; et al.; In vitro and in vivo activity of voriconazole and benznidazole combination on trypanosoma cruzi infection models; Elsevier Science; Acta Tropica; 211; 11-2020; 1-9; 105606
0001-706X
1873-6254
CONICET Digital
CONICET
Autor
Gulin, Julián Ernesto Nicolás
Eagleson, Mackenzie Anne
López Muñoz, Rodrigo A.
Solana, María Elisa
Altcheh, Jaime Marcelo
García Bournissen, Facundo
Resumen
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.