Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo

Detalhes bibliográficos
Autor(a) principal: Batista, Denise da Gama Jaén
Data de Publicação: 2011
Outros Autores: Batista, Marcos Meuser, Oliveira, Gabriel Melo de, Britto, Constança Carvalho, Rodrigues, Ana Carolina Mondaine, Stephens, Chad E., Boykin, David W., Soeiro, Maria de Nazaré Correia
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/15969
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
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spelling Batista, Denise da Gama JaénBatista, Marcos MeuserOliveira, Gabriel Melo deBritto, Constança CarvalhoRodrigues, Ana Carolina MondaineStephens, Chad E.Boykin, David W.Soeiro, Maria de Nazaré Correia2016-09-27T15:10:08Z2016-09-27T15:10:08Z2011BATISTA, Denise da Gama Jaén; et al. Combined Treatment of Heterocyclic Analogues and Benznidazole upon Trypanosoma cruzi In Vivo. Plos One, v.6, n.7, e22155, July 2011.1932-6203https://www.arca.fiocruz.br/handle/icict/1596910.1371/journal.pone.0022155engPublic Library of ScienceTrypanosoma cruziTratamentoBenznidazoleHeterocíclicos AnálogosTrypanosoma cruziBenznidazoleTreatmentHeterocyclic AnaloguesCombined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Augusta State University. Department of Chemistry and Physics. Augusta, Georgia, USA.Augusta State University. Department of Chemistry. Georgia, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Chagas disease caused by Trypanosoma cruzi is an important cause of mortality and morbidity in Latin America but no vaccines or safe chemotherapeutic agents are available. Combined therapy is envisioned as an ideal approach since it may enhance efficacy by acting upon different cellular targets, may reduce toxicity and minimize the risk of drug resistance. Therefore, we investigated the activity of benznidazole (Bz) in combination with the diamidine prodrug DB289 and in combination with the arylimidamide DB766 upon T. cruzi infection in vivo. The oral treatment of T.cruzi-infected mice with DB289 and Benznidazole (Bz) alone reduced the number of circulating parasites compared with untreated mice by about 70% and 90%, respectively. However, the combination of these two compounds decreased the parasitemia by 99% and protected against animal mortality by 100%, but without providing a parasitological cure. When Bz (p.o) was combined with DB766 (via i.p. route), at least a 99.5% decrease in parasitemia levels was observed. DB766+Bz also provided 100% protection against mice mortality while Bz alone provided about 87% protection. This combined therapy also reduced the tissular lesions induced by T. cruzi infection: Bz alone reduced GPT and CK plasma levels by about 12% and 78% compared to untreated mice group, the combination of Bz with DB766 resulted in a reduction of GPT and CK plasma levels of 56% and 91%. Cure assessment through hemocultive and PCR approaches showed that Bz did not provide a parasitological cure, however, DB766 alone or associated with Bz cured ≥13% of surviving animals.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/15969/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALdenise_batista_etal_IOC_2011.pdg.PDFdenise_batista_etal_IOC_2011.pdg.PDFapplication/pdf359570https://www.arca.fiocruz.br/bitstream/icict/15969/2/denise_batista_etal_IOC_2011.pdg.PDF68ce656d11fc956615ef20ce97effa8dMD52TEXTdenise_batista_etal_IOC_2011.pdg.PDF.txtdenise_batista_etal_IOC_2011.pdg.PDF.txtExtracted texttext/plain41568https://www.arca.fiocruz.br/bitstream/icict/15969/3/denise_batista_etal_IOC_2011.pdg.PDF.txt34f48717be7069534764173497ec6a2cMD53icict/159692018-04-02 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dc.title.pt_BR.fl_str_mv Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo
title Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo
spellingShingle Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo
Batista, Denise da Gama Jaén
Trypanosoma cruzi
Tratamento
Benznidazole
Heterocíclicos Análogos
Trypanosoma cruzi
Benznidazole
Treatment
Heterocyclic Analogues
title_short Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo
title_full Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo
title_fullStr Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo
title_full_unstemmed Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo
title_sort Combined treatment of heterocyclic analogues and benznidazole upon Trypanosoma cruzi in vivo
author Batista, Denise da Gama Jaén
author_facet Batista, Denise da Gama Jaén
Batista, Marcos Meuser
Oliveira, Gabriel Melo de
Britto, Constança Carvalho
Rodrigues, Ana Carolina Mondaine
Stephens, Chad E.
Boykin, David W.
Soeiro, Maria de Nazaré Correia
author_role author
author2 Batista, Marcos Meuser
Oliveira, Gabriel Melo de
Britto, Constança Carvalho
Rodrigues, Ana Carolina Mondaine
Stephens, Chad E.
Boykin, David W.
Soeiro, Maria de Nazaré Correia
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Batista, Denise da Gama Jaén
Batista, Marcos Meuser
Oliveira, Gabriel Melo de
Britto, Constança Carvalho
Rodrigues, Ana Carolina Mondaine
Stephens, Chad E.
Boykin, David W.
Soeiro, Maria de Nazaré Correia
dc.subject.other.pt_BR.fl_str_mv Trypanosoma cruzi
Tratamento
Benznidazole
Heterocíclicos Análogos
topic Trypanosoma cruzi
Tratamento
Benznidazole
Heterocíclicos Análogos
Trypanosoma cruzi
Benznidazole
Treatment
Heterocyclic Analogues
dc.subject.en.pt_BR.fl_str_mv Trypanosoma cruzi
Benznidazole
Treatment
Heterocyclic Analogues
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
publishDate 2011
dc.date.issued.fl_str_mv 2011
dc.date.accessioned.fl_str_mv 2016-09-27T15:10:08Z
dc.date.available.fl_str_mv 2016-09-27T15:10:08Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv BATISTA, Denise da Gama Jaén; et al. Combined Treatment of Heterocyclic Analogues and Benznidazole upon Trypanosoma cruzi In Vivo. Plos One, v.6, n.7, e22155, July 2011.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/15969
dc.identifier.issn.pt_BR.fl_str_mv 1932-6203
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pone.0022155
identifier_str_mv BATISTA, Denise da Gama Jaén; et al. Combined Treatment of Heterocyclic Analogues and Benznidazole upon Trypanosoma cruzi In Vivo. Plos One, v.6, n.7, e22155, July 2011.
1932-6203
10.1371/journal.pone.0022155
url https://www.arca.fiocruz.br/handle/icict/15969
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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