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Combination therapy using nitro compounds improves the efficacy of experimental Chagas disease treatment

Published online by Cambridge University Press:  18 June 2021

Ana Lia Mazzeti Open the ORCID record for Ana Lia Mazzeti [Opens in a new window] ,
Karolina R. Gonçalves ,
Suianne L. A. Mota ,
Dário Elias Pereira ,
Lívia de F. Diniz  and
Maria Terezinha Bahia
Ana Lia Mazzeti*
Affiliation:
Laboratório de Doenças Parasitárias, Escola de Medicina & Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Universitário Morro do Cruzeiro, Ouro Preto, MG35400-000, Brazil Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ21040-360, Brazil
Karolina R. Gonçalves
Affiliation:
Laboratório de Doenças Parasitárias, Escola de Medicina & Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Universitário Morro do Cruzeiro, Ouro Preto, MG35400-000, Brazil
Suianne L. A. Mota
Affiliation:
Laboratório de Doenças Parasitárias, Escola de Medicina & Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Universitário Morro do Cruzeiro, Ouro Preto, MG35400-000, Brazil
Dário Elias Pereira
Affiliation:
Laboratório de Doenças Parasitárias, Escola de Medicina & Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Universitário Morro do Cruzeiro, Ouro Preto, MG35400-000, Brazil
Lívia de F. Diniz
Affiliation:
Laboratório de Parasitologia Básica, Departamento de Patologia e Parasitologia, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, MG37130-001, Brazil
Maria Terezinha Bahia
Affiliation:
Laboratório de Doenças Parasitárias, Escola de Medicina & Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Universitário Morro do Cruzeiro, Ouro Preto, MG35400-000, Brazil
*
Author for correspondence: Ana Lia Mazzeti, E-mail: [email protected]; [email protected]
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Abstract

Drug combinations have been evaluated for Chagas disease in an attempt to improve efficacy and safety. In this line, the objective of this work is to assess the effects of treatment with nitro drugs combinations using benznidazole (BZ) or nifurtimox (NFX) plus the sulfone metabolite of fexinidazole (fex-SFN) in vitro and in vivo on Trypanosoma cruzi infection. The in vitro interaction of fex-SFN and BZ or NFX against infected H9c2 cells by the Y strain was classified as an additive (0.5⩾ΣFIC<4), suggesting the possibility of a dose reduction in the in vivo T. cruzi infection. Next, the effect of combining suboptimal doses was assessed in an acute model of murine T. cruzi infection. Drug combinations led to a faster suppression of parasitemia than monotherapies. Also, the associations led to higher cure levels than those in the reference treatment BZ 100 mg day−1 (57.1%) (i.e. 83.3% with BZ/fex-SFN and 75% with NFX/fex-SFN). Importantly, toxic effects resulting from the associations were not observed, according to weight gain and hepatic enzyme levels in the serum of experimental animals. Taken together, this study is a starting point to explore the potential effects of nitro drugs combinations in preclinical models of kinetoplastid-related infections.

Keywords

BenznidazoleChagas diseasechemotherapycombinationnifurtimoxnitro compoundssulfone metabolite of fexinidazoleTrypanosoma cruzi
Type
Research Article
Information
Parasitology , Volume 148 , Issue 11 , September 2021 , pp. 1320 - 1327
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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