Artículos de revistas
Pentamidine antagonizes the benznidazole's effect in vitro, and lacks of synergy in vivo: Implications about the polyamine transport as an anti-Trypanosoma cruzi target
Fecha
2016Registro en:
Experimental Parasitology, Volumen 171,
10902449
00144894
10.1016/j.exppara.2016.10.007
Autor
Seguel, Verónica
Castro, Lorena
Reigada, Chantal
Cortes, Leonel
Díaz, María V.
Miranda, Mariana R.
Pereira, Claudio A.
Lapier, Michel
Campos Estrada, Carolina
Morello Casté, Antonio
Kemmerling Weis, Ulrike
Maya Arango, Juan
López Muñoz, Rodrigo
Institución
Resumen
© 2016 Elsevier Inc.Benznidazole is the first-line drug used in treating Chagas disease, which is caused by the parasite Trypanosoma cruzi (T. cruzi). However, benznidazole has limited efficacy and several adverse reactions. Pentamidine is an antiprotozoal drug used in the treatment of leishmaniasis and African trypanosomiasis. In T. cruzi, pentamidine blocks the transport of putrescine, a precursor of trypanothione, which constitutes an essential molecule in the resistance of T. cruzi to benznidazole. In the present study, we describe the effect of the combination of benznidazole and pentamidine on isolated parasites, mammalian cells and in mice infected with T. cruzi. In isolated trypomastigotes, we performed a dose-matrix scheme of combinations, where pentamidine antagonized the effect of benznidazole, mainly at concentrations below the EC50 of pentamidine. In T. cruzi-infected mammalian cells, pentamidine reversed the effect of benznidazole (measured by qPCR). In comparison, in inf