Preclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infection

Produção científica do Laboratório de Biologia Celular.

Detalles Bibliográficos
Autores: Barbosa, Juliana Magalhães Chaves, Silva, Yasmin Pedra Rezende da, Santos, Hílton Antônio Mata dos, Pereira, Glaucia Vilar, Oliveira, Tatiana Galvão de Melo de, Ramos, Isalira Peroba Rezende, Gibaldi, Daniel, Moreira, Otacilio da Cruz, Nunes, Daniela Ferreira, Batista, Marcos Meuser, Vieira, Joseli Lannes, Daliry, Anissa, Salomão, Kelly
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:Brasil
Institución:Fundação Oswaldo Cruz (FIOCRUZ)
Repositorio:Repositório Institucional da FIOCRUZ (ARCA)
Idioma:inglés
OAI Identifier:oai:arca.fiocruz.br:icict/64633
Acceso en línea:https://arca.fiocruz.br/handle/icict/64633
Access Level:acceso abierto
Palabra clave:Chagasic chronic cardiomyopathy
Benznidazole
Amiodarone
Combination therapy
Trypanosoma cruzi
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dc.title.none.fl_str_mv Preclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infection
title Preclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infection
spellingShingle Preclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infection
Barbosa, Juliana Magalhães Chaves
Chagasic chronic cardiomyopathy
Benznidazole
Amiodarone
Combination therapy
Trypanosoma cruzi
title_short Preclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infection
title_full Preclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infection
title_fullStr Preclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infection
title_full_unstemmed Preclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infection
title_sort Preclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infection
dc.creator.none.fl_str_mv Barbosa, Juliana Magalhães Chaves
Silva, Yasmin Pedra Rezende da
Santos, Hílton Antônio Mata dos
Pereira, Glaucia Vilar
Oliveira, Tatiana Galvão de Melo de
Ramos, Isalira Peroba Rezende
Gibaldi, Daniel
Moreira, Otacilio da Cruz
Nunes, Daniela Ferreira
Batista, Marcos Meuser
Vieira, Joseli Lannes
Daliry, Anissa
Salomão, Kelly
author Barbosa, Juliana Magalhães Chaves
author_facet Barbosa, Juliana Magalhães Chaves
Silva, Yasmin Pedra Rezende da
Santos, Hílton Antônio Mata dos
Pereira, Glaucia Vilar
Oliveira, Tatiana Galvão de Melo de
Ramos, Isalira Peroba Rezende
Gibaldi, Daniel
Moreira, Otacilio da Cruz
Nunes, Daniela Ferreira
Batista, Marcos Meuser
Vieira, Joseli Lannes
Daliry, Anissa
Salomão, Kelly
author_role author
author2 Silva, Yasmin Pedra Rezende da
Santos, Hílton Antônio Mata dos
Pereira, Glaucia Vilar
Oliveira, Tatiana Galvão de Melo de
Ramos, Isalira Peroba Rezende
Gibaldi, Daniel
Moreira, Otacilio da Cruz
Nunes, Daniela Ferreira
Batista, Marcos Meuser
Vieira, Joseli Lannes
Daliry, Anissa
Salomão, Kelly
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.en.none.fl_str_mv Chagasic chronic cardiomyopathy
Benznidazole
Amiodarone
Combination therapy
Trypanosoma cruzi
topic Chagasic chronic cardiomyopathy
Benznidazole
Amiodarone
Combination therapy
Trypanosoma cruzi
description Produção científica do Laboratório de Biologia Celular.
publishDate 2024
dc.date.accessioned.fl_str_mv 2024-06-24T17:02:01Z
dc.date.available.fl_str_mv 2024-06-24T17:02:01Z
dc.date.issued.fl_str_mv 2024
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv BARBOSA, Juliana Magalhães Chaves et al. Preclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infection. Biomedicine and Pharmacotherapy, v. 175, p. 1-22, June 2024.
dc.identifier.uri.fl_str_mv https://arca.fiocruz.br/handle/icict/64633
dc.identifier.issn.none.fl_str_mv 0753-3322
dc.identifier.doi.none.fl_str_mv 10.1016/j.biopha.2024.116742
identifier_str_mv BARBOSA, Juliana Magalhães Chaves et al. Preclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infection. Biomedicine and Pharmacotherapy, v. 175, p. 1-22, June 2024.
0753-3322
10.1016/j.biopha.2024.116742
url https://arca.fiocruz.br/handle/icict/64633
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 Elsevier
publisher.none.fl_str_mv Elsevier
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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spelling 2024-06-24T17:02:01Z2024-06-24T17:02:01Z2024BARBOSA, Juliana Magalhães Chaves et al. Preclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infection. Biomedicine and Pharmacotherapy, v. 175, p. 1-22, June 2024.0753-3322https://arca.fiocruz.br/handle/icict/6463310.1016/j.biopha.2024.116742Produção científica do Laboratório de Biologia Celular.Produção científica do Laboratório de Biologia das Interações.Produção científica do Laboratório de Fisiopatologia Clínica e Experimental.Produção científica do Laboratório de Ultraestrutura Celular.Produção científica do Laboratório de Virologia e Parasitologia Molecular.This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Instituto Oswaldo Cruz (IOC/Fiocruz).Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Fisiopatologia Clínica e Experimental. 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 das Interações. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Faculdade de Farmácia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Pesquisas de Produtos Naturais Walter Mors. Laboratório de Análise e Desenvolvimento de Inibidores Enzimáticos. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Pesquisa de Produtos Naturais Walters Mors. Laboratório Multiusuário de Análises por Ressonância Magnética Nuclear. 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 Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Centro Nacional de Biologia Estrutural e Bioimagem. 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 Virologia e Parasitologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia e Parasitologia Molecular. 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 das Interações. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Fisiopatologia Clínica e Experimental. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Chagasic chronic cardiomyopathy (CCC) is the primary clinical manifestation of Chagas disease (CD), caused by Trypanosoma cruzi. Current therapeutic options for CD are limited to benznidazole (Bz) and nifurtimox. Amiodarone (AMD) has emerged as most effective drug for treating the arrhythmic form of CCC. To address the effects of Bz and AMD we used a preclinical model of CCC. Female C57BL/6 mice were infected with T. cruzi and subjected to oral treatment for 30 consecutive days, either as monotherapy or in combination. AMD in monotherapy decreased the prolonged QTc interval, the incidence of atrioventricular conduction disorders and cardiac hypertrophy. However, AMD monotherapy did not impact parasitemia, parasite load, TNF concentration and production of reactive oxygen species (ROS) in cardiac tissue. Alike Bz therapy, the combination of Bz and AMD (Bz/AMD), improved cardiac electric abnormalities detected T. cruzi-infected mice such as decrease in heart rates, enlargement of PR and QTc intervals and increased incidence of atrioventricular block and sinus arrhythmia. Further, Bz/AMD therapy ameliorated the ventricular function and reduced parasite burden in the cardiac tissue and parasitemia to a degree comparable to Bz monotherapy. Importantly, Bz/AMD treatment efficiently reduced TNF concentration in the cardiac tissue and plasma and had beneficial effects on immunological abnormalities. Moreover, in the cardiac tissue Bz/AMD therapy reduced fibronectin and collagen deposition, mitochondrial damage and production of ROS, and improved sarcomeric and gap junction integrity. Our study underlines the potential of the Bz/AMD therapy, as we have shown that combination increased efficacy in the treatment of CCC.engElsevierPreclinical evaluation of combined therapy with amiodarone and low-dose benznidazole in a mouse model of chronic Trypanosoma cruzi infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleChagasic chronic cardiomyopathyBenznidazoleAmiodaroneCombination therapyTrypanosoma cruziinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZBarbosa, Juliana Magalhães ChavesSilva, Yasmin Pedra Rezende daSantos, Hílton Antônio Mata dosPereira, Glaucia VilarOliveira, Tatiana Galvão de Melo deRamos, Isalira Peroba RezendeGibaldi, DanielMoreira, Otacilio da CruzNunes, Daniela FerreiraBatista, Marcos MeuserVieira, Joseli LannesDaliry, AnissaSalomão, KellyLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://arca.fiocruz.br/bitstreams/ec3c4aa0-0cb4-4237-85d8-2cb099fc7a5d/download5a560609d32a3863062d77ff32785d58MD51falseAnonymousREADORIGINALve_Juliana_Barbosa_etal_IOC_2024.pdfve_Juliana_Barbosa_etal_IOC_2024.pdfapplication/pdf23162030https://arca.fiocruz.br/bitstreams/e22ad06f-545b-429f-bdbd-784baf92f5f2/downloadaadd9962ddcd47801b80972812f5997dMD52trueAnonymousREADTHUMBNAILcapa_Juliana_Barbosa_etal_IOC_2024.jpgcapa_Juliana_Barbosa_etal_IOC_2024.jpgCapaimage/jpeg2109290https://arca.fiocruz.br/bitstreams/09f3b9c4-bd53-4123-9393-d8b9649410e0/download8e3a0f89fc73c4b6f9c355f3dc7e3de1MD53falseAnonymousREADve_Juliana_Barbosa_etal_IOC_2024.pdf.jpgve_Juliana_Barbosa_etal_IOC_2024.pdf.jpgGenerated Thumbnailimage/jpeg36429https://arca.fiocruz.br/bitstreams/e36e239a-19db-4c9c-9c1a-5121709d22a6/download1abed655b1aed40ca5e582fbdf689d48MD511falseAnonymousREADTEXTve_Juliana_Barbosa_etal_IOC_2024.pdf.txtve_Juliana_Barbosa_etal_IOC_2024.pdf.txtExtracted texttext/plain100552https://arca.fiocruz.br/bitstreams/df2c973a-3d1d-48c7-a9ab-c468250a560a/downloadc181fad0c0d4634972abd51deaea0cbbMD510falseAnonymousREADicict/646332025-12-10 15:10:22.203open.accessoai:arca.fiocruz.br:icict/64633https://arca.fiocruz.brRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352025-12-10T18:10:22Repositório Institucional da FIOCRUZ (ARCA) - 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