Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis

Detalhes bibliográficos
Autor(a) principal: Oliveira, Flora Magno de Jesus
Data de Publicação: 2020
Outros Autores: Albuquerque, Cassiano Felippe Gonçalves de, Moraes, Isabel Matos Medeiros de, Reis, Patrícia Alves, Rocha, Vinicius Novaes, Bozza, Patrícia T., Silva, Adriana Ribeiro, Faria Neto, Hugo Caire C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/44844
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
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spelling Oliveira, Flora Magno de JesusAlbuquerque, Cassiano Felippe Gonçalves deMoraes, Isabel Matos Medeiros deReis, Patrícia AlvesRocha, Vinicius NovaesBozza, Patrícia T.Silva, Adriana RibeiroFaria Neto, Hugo Caire C.2020-12-11T17:47:16Z2020-12-11T17:47:16Z2020OLIVEIRA, Flora Magno de Jesus et al. Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis. Mediators of Inflammation, v. 2020, Article ID 1839762, p. 1-11, 2020.0962-9351https://www.arca.fiocruz.br/handle/icict/4484410.1155/2020/18397621466-1861engHindawiSinvastatinaPós-tratamentoInflamaçãoControleDepuração bacterianaSepse experimentalSimvastatinPosttreatment ControlsInflammationBacterial ClearanceExperimental SepsisSimvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Rio de Janeiro. Instituto Biomédico. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal de Juiz de Fora. Departamento de Medicina Veterinária. Laboratório de Patologia e Histologia Veterinária. Juiz de Fora, MG, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Sepsis is characterized by a life-threatening organ dysfunction caused by an unbalanced host response to microbe infection that can lead to death. Besides being currently the leading cause of death in intensive care units worldwide, sepsis can also induce long-term consequences among survivors, such as cognitive impairment. Statins (lipid-lowering drugs widely used to treat dyslipidemia) have been shown to possess pleiotropic anti-inflammatory and antimicrobial effects. These drugs act inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, the limiting step in cholesterol biosynthesis. In this work, we evaluated the therapeutic effects of simvastatin in an animal model of sepsis. In previous study from our group, statin pretreatment avoided cognitive damage and neuroinflammation in sepsis survivors. Herein, we focused on acute inflammation where sepsis was induced by cecal ligation and puncture (CLP), and the animals were treated with simvastatin (2 mg/kg) 6 h after surgery. We measured plasma biochemical markers of organ dysfunction, cell migration, cell activation, bacterial elimination, production of nitric oxide 24 h after CLP, survival rate for 7 days, and cognitive impairment 15 days after CLP. One single administration of simvastatin 6 h after CLP was able to prevent both liver and kidney dysfunction. In addition, this drug decreased cell accumulation in the peritoneum as well as the levels of TNF-α, MIF, IL-6, and IL-1β. Simvastatin diminished the number of bacterial colony forming units (CFU) and increased the production of nitric oxide production in the peritoneum. Simvastatin treatment increased survival for the first 24 h, but it did not alter survival rate at the end of 7 days. Our results showed that posttreatment with simvastatin hampered organ dysfunction, increased local production of nitric oxide, improved bacterial clearance, and modulated inflammation in a relevant model of sepsis.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/44844/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALFloraOliveira_AdrianaSilva_etal_IOC_2020.pdfFloraOliveira_AdrianaSilva_etal_IOC_2020.pdfapplication/pdf1994544https://www.arca.fiocruz.br/bitstream/icict/44844/2/FloraOliveira_AdrianaSilva_etal_IOC_2020.pdf9fa83f441706d9850517d5066f8efa49MD52TEXTFloraOliveira_AdrianaSilva_etal_IOC_2020.pdf.txtFloraOliveira_AdrianaSilva_etal_IOC_2020.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis
title Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis
spellingShingle Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis
Oliveira, Flora Magno de Jesus
Sinvastatina
Pós-tratamento
Inflamação
Controle
Depuração bacteriana
Sepse experimental
Simvastatin
Posttreatment Controls
Inflammation
Bacterial Clearance
Experimental Sepsis
title_short Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis
title_full Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis
title_fullStr Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis
title_full_unstemmed Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis
title_sort Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis
author Oliveira, Flora Magno de Jesus
author_facet Oliveira, Flora Magno de Jesus
Albuquerque, Cassiano Felippe Gonçalves de
Moraes, Isabel Matos Medeiros de
Reis, Patrícia Alves
Rocha, Vinicius Novaes
Bozza, Patrícia T.
Silva, Adriana Ribeiro
Faria Neto, Hugo Caire C.
author_role author
author2 Albuquerque, Cassiano Felippe Gonçalves de
Moraes, Isabel Matos Medeiros de
Reis, Patrícia Alves
Rocha, Vinicius Novaes
Bozza, Patrícia T.
Silva, Adriana Ribeiro
Faria Neto, Hugo Caire C.
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Oliveira, Flora Magno de Jesus
Albuquerque, Cassiano Felippe Gonçalves de
Moraes, Isabel Matos Medeiros de
Reis, Patrícia Alves
Rocha, Vinicius Novaes
Bozza, Patrícia T.
Silva, Adriana Ribeiro
Faria Neto, Hugo Caire C.
dc.subject.other.pt_BR.fl_str_mv Sinvastatina
Pós-tratamento
Inflamação
Controle
Depuração bacteriana
Sepse experimental
topic Sinvastatina
Pós-tratamento
Inflamação
Controle
Depuração bacteriana
Sepse experimental
Simvastatin
Posttreatment Controls
Inflammation
Bacterial Clearance
Experimental Sepsis
dc.subject.en.pt_BR.fl_str_mv Simvastatin
Posttreatment Controls
Inflammation
Bacterial Clearance
Experimental Sepsis
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-12-11T17:47:16Z
dc.date.available.fl_str_mv 2020-12-11T17:47:16Z
dc.date.issued.fl_str_mv 2020
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 OLIVEIRA, Flora Magno de Jesus et al. Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis. Mediators of Inflammation, v. 2020, Article ID 1839762, p. 1-11, 2020.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/44844
dc.identifier.issn.pt_BR.fl_str_mv 0962-9351
dc.identifier.doi.none.fl_str_mv 10.1155/2020/1839762
dc.identifier.eissn.none.fl_str_mv 1466-1861
identifier_str_mv OLIVEIRA, Flora Magno de Jesus et al. Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis. Mediators of Inflammation, v. 2020, Article ID 1839762, p. 1-11, 2020.
0962-9351
10.1155/2020/1839762
1466-1861
url https://www.arca.fiocruz.br/handle/icict/44844
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 Hindawi
publisher.none.fl_str_mv Hindawi
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
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