Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas' Heart Disease

Detalhes bibliográficos
Autor(a) principal: Pereira, Glaucia Vilar
Data de Publicação: 2016
Outros Autores: Pereira, Isabela Resende, Ruivo, Leonardo Alexandre de Souza, Moreira, Otacilio Cruz, Silva, Andrea Alice da, Britto, Constança, Lannes-Vieira, Joseli
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/16443
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.
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spelling Pereira, Glaucia VilarPereira, Isabela ResendeRuivo, Leonardo Alexandre de SouzaMoreira, Otacilio CruzSilva, Andrea Alice daBritto, ConstançaLannes-Vieira, Joseli2016-12-06T14:46:08Z2016-12-06T14:46:08Z2016PEREIRA, Glaucia Vilar; et al Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas’ Heart Disease. Antimicrobial Agents and Chemotherapy, v.60, n.7, p.4297-4309, July 2016.0066-4804https://www.arca.fiocruz.br/handle/icict/1644310.1128/AAC.02123-151098-6596engAmerican Society for MicrobiologyDoença de ChagasCardiomiopatia ChagásicaTratamentoChronic chagasic cardiomyopathyBenznidazolePentoxifyllineChagas’ Heart DiseaseCombination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas' Heart Diseaseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Faculdade de Medicina. Departamento de Patologia. Niterói, 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 das Interações. Rio de Janeiro, RJ, Brasil.Chronic chagasic cardiomyopathy (CCC) progresses with parasite persistence, fibrosis, and electrical alterations associated with an unbalanced immune response such as high plasma levels of tumor necrosis factor (TNF) and nitric oxide (NO). Presently, the available treatments only mitigate the symptoms of CCC. To improve CCC prognosis, we interfered with the parasite load and unbalanced immune response using the trypanocidal drug benznidazole (Bz) and the immunoregulator pentoxifylline (PTX). C57BL/6 mice chronically infected with the Colombian strain of Trypanosoma cruzi and with signs of CCC were treated for 30 days with a suboptimal dose of Bz (25 mg/kg of body weight), PTX (20 mg/kg), or their combination (Bz plus PTX) and analyzed for electrocardiographic, histopathological, and immunological changes. Bz (76%) and Bz-plus-PTX (79%) therapies decreased parasite loads. Although the three therapies reduced myocarditis and fibrosis and ameliorated electrical alterations, only Bz plus PTX restored normal heart rate-corrected QT (QTc) intervals. Bz-plus-PTX-treated mice presented complementary effects of Bz and PTX, which reduced TNF expression (37%) in heart tissue and restored normal TNF receptor 1 expression on CD8(+) T cells, respectively. Bz (85%) and PTX (70%) therapies reduced the expression of inducible nitric oxide synthase (iNOS/NOS2) in heart tissue, but only Bz (58%) reduced NO levels in serum. These effects were more pronounced after Bz-plus-PTX therapy. Moreover, 30 to 50 days after treatment cessation, reductions of the prolonged QTc and QRS intervals were sustained in Bz-plus-PTX-treated mice. Our findings support the importance of interfering with the etiological agent and immunological abnormalities to improve CCC prognosis, opening an opportunity for a better quality of life for Chagas' disease (CD) patients.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/16443/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALglaucia_pereira_etal_IOC_2016.pdfglaucia_pereira_etal_IOC_2016.pdfapplication/pdf1715795https://www.arca.fiocruz.br/bitstream/icict/16443/2/glaucia_pereira_etal_IOC_2016.pdf37fc81d5397e81ab69a5272837cf7d49MD52TEXTglaucia_pereira_etal_IOC_2016.pdf.txtglaucia_pereira_etal_IOC_2016.pdf.txtExtracted texttext/plain80346https://www.arca.fiocruz.br/bitstream/icict/16443/3/glaucia_pereira_etal_IOC_2016.pdf.txt4430aad2bb7e1e539fd38540d0015e3aMD53icict/164432018-08-15 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dc.title.pt_BR.fl_str_mv Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas' Heart Disease
title Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas' Heart Disease
spellingShingle Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas' Heart Disease
Pereira, Glaucia Vilar
Doença de Chagas
Cardiomiopatia Chagásica
Tratamento
Chronic chagasic cardiomyopathy
Benznidazole
Pentoxifylline
Chagas’ Heart Disease
title_short Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas' Heart Disease
title_full Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas' Heart Disease
title_fullStr Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas' Heart Disease
title_full_unstemmed Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas' Heart Disease
title_sort Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas' Heart Disease
author Pereira, Glaucia Vilar
author_facet Pereira, Glaucia Vilar
Pereira, Isabela Resende
Ruivo, Leonardo Alexandre de Souza
Moreira, Otacilio Cruz
Silva, Andrea Alice da
Britto, Constança
Lannes-Vieira, Joseli
author_role author
author2 Pereira, Isabela Resende
Ruivo, Leonardo Alexandre de Souza
Moreira, Otacilio Cruz
Silva, Andrea Alice da
Britto, Constança
Lannes-Vieira, Joseli
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Pereira, Glaucia Vilar
Pereira, Isabela Resende
Ruivo, Leonardo Alexandre de Souza
Moreira, Otacilio Cruz
Silva, Andrea Alice da
Britto, Constança
Lannes-Vieira, Joseli
dc.subject.other.pt_BR.fl_str_mv Doença de Chagas
Cardiomiopatia Chagásica
Tratamento
topic Doença de Chagas
Cardiomiopatia Chagásica
Tratamento
Chronic chagasic cardiomyopathy
Benznidazole
Pentoxifylline
Chagas’ Heart Disease
dc.subject.en.pt_BR.fl_str_mv Chronic chagasic cardiomyopathy
Benznidazole
Pentoxifylline
Chagas’ Heart Disease
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ, Brasil.
publishDate 2016
dc.date.accessioned.fl_str_mv 2016-12-06T14:46:08Z
dc.date.available.fl_str_mv 2016-12-06T14:46:08Z
dc.date.issued.fl_str_mv 2016
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 PEREIRA, Glaucia Vilar; et al Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas’ Heart Disease. Antimicrobial Agents and Chemotherapy, v.60, n.7, p.4297-4309, July 2016.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/16443
dc.identifier.issn.pt_BR.fl_str_mv 0066-4804
dc.identifier.doi.none.fl_str_mv 10.1128/AAC.02123-15
dc.identifier.eissn.none.fl_str_mv 1098-6596
identifier_str_mv PEREIRA, Glaucia Vilar; et al Combination Chemotherapy with Suboptimal Doses of Benznidazole and Pentoxifylline Sustains Partial Reversion of Experimental Chagas’ Heart Disease. Antimicrobial Agents and Chemotherapy, v.60, n.7, p.4297-4309, July 2016.
0066-4804
10.1128/AAC.02123-15
1098-6596
url https://www.arca.fiocruz.br/handle/icict/16443
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 American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
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)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/16443/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/16443/2/glaucia_pereira_etal_IOC_2016.pdf
https://www.arca.fiocruz.br/bitstream/icict/16443/3/glaucia_pereira_etal_IOC_2016.pdf.txt
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