5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethality

Detalhes bibliográficos
Autor(a) principal: Hohmann, Miriam S. N.
Data de Publicação: 2013
Outros Autores: Cardoso, Renato D. R., Pinho-Ribeiro, Felipe A., Crespigio, Jefferson, Cunha, Thiago M., Alves-Filho, José C., Silva, Rosiane Valeriano da, Pinge-Filho, Phileno, Ferreira, Sergio H., Cunha, Fernando Q., Casagrande, Rubia, Verri Jr, Waldiceu Aparecido
Tipo de documento: Artigo
Idioma: por
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/15596
Resumo: This work was supported by grants from SETI/Fundação Araucária, Paraná State Government, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil.
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spelling Hohmann, Miriam S. N.Cardoso, Renato D. R.Pinho-Ribeiro, Felipe A.Crespigio, JeffersonCunha, Thiago M.Alves-Filho, José C.Silva, Rosiane Valeriano daPinge-Filho, PhilenoFerreira, Sergio H.Cunha, Fernando Q.Casagrande, RubiaVerri Jr, Waldiceu Aparecido2016-09-02T15:50:44Z2016-09-02T15:50:44Z2013HOHMANN, Miriam S. N. et al. 5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethality. BioMed Research International, v. 2013, p. 1-13, 2013.2314-6141https://www.arca.fiocruz.br/handle/icict/1559610.1155/2013/627046This work was supported by grants from SETI/Fundação Araucária, Paraná State Government, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil.Universidade de São Paulo. Faculdade de Medicina de Ribeirão Preto. Departamento de Farmacologia. Ribeirão Preto, SP, Brasil.Universidade Estadual de Londrina. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Patologia. Londrina, PR, Brasil.5-Lipoxygenase (5-LO) converts arachidonic acid into leukotrienes (LTs) and is involved in inflammation. At present, the participation of 5-LO in acetaminophen (APAP)-induced hepatotoxicity and liver damage has not been addressed. 5-LO deficient (5-LO−/−) mice and background wild type mice were challenged with APAP (0.3–6 g/kg) or saline. The lethality, liver damage, neutrophil and macrophage recruitment, LTB4, cytokine production, and oxidative stress were assessed. APAP induced a dose-dependent mortality, and the dose of 3 g/kg was selected for next experiments. APAP induced LTB4 production in the liver, the primary target organ in APAP toxicity. Histopathological analysis revealed that 5-LO−/− mice presented reduced APAP-induced liver necrosis and inflammation compared with WT mice. APAP-induced lethality, increase of plasma levels of aspartate aminotransferase and alanine aminotransferase, liver cytokine (IL-1β, TNF-α, IFN-γ, and IL-10), superoxide anion, and thiobarbituric acid reactive substances production, myeloperoxidase and N-acetyl-β-D-glucosaminidase activity, Nrf2 and gp91phox mRNA expression, and decrease of reduced glutathione and antioxidant capacity measured by 2,2′-azinobis(3-ethylbenzothiazoline 6-sulfonate) assay were prevented in 5-LO−/− mice compared to WT mice. Therefore, 5-LO deficiency resulted in reduced mortality due to reduced liver inflammatory and oxidative damage, suggesting 5-LO is a promising target to reduce APAP-induced lethality and liver inflammatory/oxidative damage.porChun-MingWong5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethalityinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article5-Lipoxygenase DeficiencyArachidonic acidAcetaminophen-InducedHepatotoxicityÁcido AraquidônicoAcetaminofeninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83074https://www.arca.fiocruz.br/bitstream/icict/15596/1/license.txt0271fb68963c017aa933c7aff60379f4MD51ORIGINAL5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality.pdf5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and 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dc.title.pt_BR.fl_str_mv 5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethality
title 5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethality
spellingShingle 5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethality
Hohmann, Miriam S. N.
5-Lipoxygenase Deficiency
Arachidonic acid
Acetaminophen-Induced
Hepatotoxicity
Ácido Araquidônico
Acetaminofen
title_short 5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethality
title_full 5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethality
title_fullStr 5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethality
title_full_unstemmed 5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethality
title_sort 5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethality
author Hohmann, Miriam S. N.
author_facet Hohmann, Miriam S. N.
Cardoso, Renato D. R.
Pinho-Ribeiro, Felipe A.
Crespigio, Jefferson
Cunha, Thiago M.
Alves-Filho, José C.
Silva, Rosiane Valeriano da
Pinge-Filho, Phileno
Ferreira, Sergio H.
Cunha, Fernando Q.
Casagrande, Rubia
Verri Jr, Waldiceu Aparecido
author_role author
author2 Cardoso, Renato D. R.
Pinho-Ribeiro, Felipe A.
Crespigio, Jefferson
Cunha, Thiago M.
Alves-Filho, José C.
Silva, Rosiane Valeriano da
Pinge-Filho, Phileno
Ferreira, Sergio H.
Cunha, Fernando Q.
Casagrande, Rubia
Verri Jr, Waldiceu Aparecido
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Hohmann, Miriam S. N.
Cardoso, Renato D. R.
Pinho-Ribeiro, Felipe A.
Crespigio, Jefferson
Cunha, Thiago M.
Alves-Filho, José C.
Silva, Rosiane Valeriano da
Pinge-Filho, Phileno
Ferreira, Sergio H.
Cunha, Fernando Q.
Casagrande, Rubia
Verri Jr, Waldiceu Aparecido
dc.subject.en.pt_BR.fl_str_mv 5-Lipoxygenase Deficiency
Arachidonic acid
Acetaminophen-Induced
topic 5-Lipoxygenase Deficiency
Arachidonic acid
Acetaminophen-Induced
Hepatotoxicity
Ácido Araquidônico
Acetaminofen
dc.subject.en.En.fl_str_mv Hepatotoxicity
dc.subject.decs.pt_BR.fl_str_mv Ácido Araquidônico
Acetaminofen
description This work was supported by grants from SETI/Fundação Araucária, Paraná State Government, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil.
publishDate 2013
dc.date.issued.fl_str_mv 2013
dc.date.accessioned.fl_str_mv 2016-09-02T15:50:44Z
dc.date.available.fl_str_mv 2016-09-02T15:50:44Z
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 HOHMANN, Miriam S. N. et al. 5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethality. BioMed Research International, v. 2013, p. 1-13, 2013.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/15596
dc.identifier.issn.pt_BR.fl_str_mv 2314-6141
dc.identifier.doi.pt_BR.fl_str_mv 10.1155/2013/627046
identifier_str_mv HOHMANN, Miriam S. N. et al. 5-Lipoxygenase deficiency reduces Acetaminophen-Induced hepatotoxicity and lethality. BioMed Research International, v. 2013, p. 1-13, 2013.
2314-6141
10.1155/2013/627046
url https://www.arca.fiocruz.br/handle/icict/15596
dc.language.iso.fl_str_mv por
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Chun-MingWong
publisher.none.fl_str_mv Chun-MingWong
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
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