Time and dose-dependence evaluation of nitroheterocyclic drugs for improving efficacy following Trypanosoma cruzi infection : a pre-clinical study.

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dc.contributor.authorMazzeti, Ana Lia
dc.contributor.authorDiniz, Lívia de Figueiredo
dc.contributor.authorGonçalves, Karolina Ribeiro
dc.contributor.authorNascimento, Álvaro Fernando da Silva do
dc.contributor.authorSpósito, Pollyanna Álvaro
dc.contributor.authorMosqueira, Vanessa Carla Furtado
dc.contributor.authorCoelho, George Luiz Lins Machado
dc.contributor.authorRibeiro, Isabela
dc.contributor.authorBahia, Maria Terezinha
dc.date.accessioned2018-05-04T13:14:57Z
dc.date.available2018-05-04T13:14:57Z
dc.date.issued2018
dc.description.abstractBenznidazole and nifurtimox-treatments regimens currently used in human are supported by very limited experimental data. This study was designed to evaluate the time and dose dependence for efficacy of the most important nitroheterocyclic drugs in use for Chagas disease. In order to evaluate time dependence, Y strain-infected mice received benznidazole for a total of 1, 3, 7, 10, 20, and 40 days. Treatment courses of 3–10-day were effective in clearing parasitaemia and suppressing mortality, but parasitological cure was not achieved. Extending the treatments to 20 or 40 days clearly improved benznidazole efficacy. The 20-day treatment induced cure in 57.1% of Y strain infections (partially drug resistant) but failed to cure Colombian strain infections (full drug resistant), while the 40-day treatment resulted in cure of 100% of Y and 50% of Colombian strain infected mice. The increased cure rates in T. cruzi infected animals that received nifurtimox for 40 days confirm the relationship between the length of treatment and efficacy. An improvement in efficacy was observed with increasing benznidazole doses; cure was verified in 28.6% (75 mg/kg), 57.1% (100 mg/kg) and 80% (300 mg/kg). Overall, these nonclinical study data provide evidence that the efficacy of benznidazole is dose and time dependent. These findings may be relevant for optimizing treatment of human Chagas disease.pt_BR
dc.identifier.citationMAZZETI, A. L. et al. Time and dose-dependence evaluation of nitroheterocyclic drugs for improving efficacy following Trypanosoma cruzi infection : a pre-clinical study. Biochemical Pharmacology, v. 148, p. 213-221, 2018. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0006295218300054?via%3Dihub>. Acesso em: 05 abr. 2018.pt_BR
dc.identifier.issn00062952
dc.identifier.urihttp://www.repositorio.ufop.br/handle/123456789/9900
dc.identifier.uri2https://www.sciencedirect.com/science/article/pii/S0006295218300054?via%3Dihubpt_BR
dc.language.isoen_USpt_BR
dc.rightsrestritopt_BR
dc.subjectTrypanosoma cruzipt_BR
dc.subjectBenznidazolept_BR
dc.subjectChagas disease chemotherapypt_BR
dc.subjectNitroheterocyclic drugspt_BR
dc.titleTime and dose-dependence evaluation of nitroheterocyclic drugs for improving efficacy following Trypanosoma cruzi infection : a pre-clinical study.pt_BR
dc.typeArtigo publicado em periodicopt_BR
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