Experimental combination therapy with low doses of Benznidazole and Allopurinol on chronic T. cruzi infection

SCALISE M.LUJAN; BUA JAQUELINE; RIARTE ADELINA; ALARCON M.MICAELA; BENATAR ALEJAANDRO; FICHERA, LAURA E.; RIAL, MARCELA S.; ESTEVA, MÓNICA I.; PRADO NILDA

PARASITOLOGY

CAMBRIDGE UNIV PRESS

Lugar: Cambridge; Año: 2018 vol. 146 p. 305 - 313

0031-1820

The aim of this study was to evaluate the effectiveness of low doses of benznidazole (BNZ) on continuous administration (BNZc), combined with allopurinol (ALO), in C57BL/6J and C3H/HeN mice, infected with T. cruzi Nicaragua and T. cruzi Sylvio-X10/4 strain. C57BL/6J was also treated with BNZ administered intermittently (BNZit). The drug therapy started 3 months post infection (pi) in the chronic phase of mice with heart disease progression, followed-up at 6 months pi. C57BL/6J treated with BNZc was also monitored up to 12 months pi (serology and electrocardiogram). ALO showed only synergy with lowest dose of BNZ. Significant reductions in antibody titers, reduction of parasitic loads and no cardiac abnormalities were observed after treatments. A clear parasitic effect was achieved in all models with low doses of BNZ, and a 25% reduction of the conventional dose had an outstanding efficiency to inhibit the development of the pathology. The electrocardigrams showed severe electrical abnormalities in infected mice, which were not observed either with BNZc or BNZit . C57BL/6J allowed to clearly define a chronic phase, and through a series of reproducible efficacy indicators, to be considered a good preclinical model, similar to other models described in the literature.