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Experimental combination therapy using low doses of benznidazole and allopurinol in mouse models of Trypanosoma cruzi chronic infection

Published online by Cambridge University Press:  10 October 2018

Marcela Silvina Rial ,
María Luján Scalise ,
Micaela López Alarcón ,
Mónica Inés Esteva ,
Jacqueline Búa ,
Alejandro Francisco Benatar ,
Nilda Graciela Prado ,
Adelina Rosa Riarte  and
Laura Edith Fichera Open the ORCID record for Laura Edith Fichera [Opens in a new window]
Marcela Silvina Rial
Affiliation:
Instituto Nacional de Parasitología ‘Dr Mario Fatala Chaben’, ANLIS CG Malbrán, Ministerio de Salud. Avenida Paseo Colón 568 ZIP Code: 1063, Buenos Aires, Argentina
María Luján Scalise
Affiliation:
Instituto Nacional de Parasitología ‘Dr Mario Fatala Chaben’, ANLIS CG Malbrán, Ministerio de Salud. Avenida Paseo Colón 568 ZIP Code: 1063, Buenos Aires, Argentina
Micaela López Alarcón
Affiliation:
Instituto Nacional de Parasitología ‘Dr Mario Fatala Chaben’, ANLIS CG Malbrán, Ministerio de Salud. Avenida Paseo Colón 568 ZIP Code: 1063, Buenos Aires, Argentina
Mónica Inés Esteva
Affiliation:
Instituto Nacional de Parasitología ‘Dr Mario Fatala Chaben’, ANLIS CG Malbrán, Ministerio de Salud. Avenida Paseo Colón 568 ZIP Code: 1063, Buenos Aires, Argentina
Jacqueline Búa
Affiliation:
Instituto Nacional de Parasitología ‘Dr Mario Fatala Chaben’, ANLIS CG Malbrán, Ministerio de Salud. Avenida Paseo Colón 568 ZIP Code: 1063, Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2290 ZIP Code: 1425, Buenos Aires, Argentina
Alejandro Francisco Benatar
Affiliation:
INGEBI-CONICET, Vuelta de Obligado 2490 ZIP Code: 1428, Buenos Aires, Argentina
Nilda Graciela Prado
Affiliation:
Instituto Nacional de Parasitología ‘Dr Mario Fatala Chaben’, ANLIS CG Malbrán, Ministerio de Salud. Avenida Paseo Colón 568 ZIP Code: 1063, Buenos Aires, Argentina
Adelina Rosa Riarte
Affiliation:
Instituto Nacional de Parasitología ‘Dr Mario Fatala Chaben’, ANLIS CG Malbrán, Ministerio de Salud. Avenida Paseo Colón 568 ZIP Code: 1063, Buenos Aires, Argentina
Laura Edith Fichera*
Affiliation:
Instituto Nacional de Parasitología ‘Dr Mario Fatala Chaben’, ANLIS CG Malbrán, Ministerio de Salud. Avenida Paseo Colón 568 ZIP Code: 1063, Buenos Aires, Argentina Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz 2290 ZIP Code: 1425, Buenos Aires, Argentina
*
Author for correspondence: Laura Edith Fichera, E-mail: [email protected]
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Abstract

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.

Keywords

BenznidazoleChagas disease treatmentexperimental chronic T. cruzi infectionmouse modelsTrypanosoma cruzi
Type
Research Article
Information
Parasitology , Volume 146 , Issue 3 , March 2019 , pp. 305 - 313
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Copyright
Copyright © Cambridge University Press 2018 

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Footnotes

*

The authors contributed equally in this study

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