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Title: Experimental combination therapy using low doses of benznidazole and allopurinol in mouse models of Trypanosoma cruzi chronic infection
Authors: Rial, Marcela Silvina 
Scalise, María Luján 
López Alarcón, Micaela 
Esteva, Mónica Inés 
Bua, Jacqueline 
Benatar, Alejandro Francisco 
Prado, Nilda Graciela 
Riarte, Adelina Rosa 
Fichera, Laura Edith 
Keywords: Tratamiento Enfermedad de Chagas;Trypanosoma cruzi
Issue Date: 2019
Journal: Parasitology 
This study evaluated 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 Trypanosoma cruzi Nicaragua strain and T. cruzi Sylvio-X10/4 clone. TcN-C57BL/6J was also treated with intermittent doses of BNZ (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. TcN-C57BL/6J treated with BNZc was also monitored up to 12 months pi by serology and electrocardiogram. These mice showed severe electrical abnormalities, which were not observed after BNZc or BNZit. ALO only showed positive interaction with the lowest dose of BNZ. A clear parasitic effect, with significant reductions in antibody titres and parasitic loads, was achieved in all models with low doses of BNZ, and a 25% reduction of the conventional dose showed more efficacy to inhibit the development of the pathology. However, BNZ 75 showed partial efficacy in the TcSylvio-X10/4-C3H/HeN model. In our experimental designs, C57BL/6J allowed to clearly define a chronic phase, and through reproducible efficacy indicators, it can be considered a good preclinical model.
DOI: 10.1017/S0031182018001567
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