Combination therapy using nitro compounds improves the efficacy of experimental Chagas disease treatment.
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Date
2021
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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 classi-
fied 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 parasit-
emia 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.
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Keywords
Benznidazole, Trypanosoma cruzi, Chagas disease, Chemotherapy, Combination
Citation
MAZZETI, A. L. et al. Combination therapy using nitro compounds improves the efficacy of experimental Chagas disease treatment. Parasitology, v. 148, p. 1320-1327, 2021. Disponível em: <https://www.cambridge.org/core/journals/parasitology/article/abs/combination-therapy-using-nitro-compounds-improves-the-efficacy-of-experimental-chagas-disease-treatment/4663987A4596FBE968EA04D2C0F14E06>. Acesso em: 11 out. 2022.