Modulation of Cytochrome P450 2A5 Activity by Lipopolysaccharide: Low-Dose Effects and Non-Monotonic Dose-Response Relationship

Detalhes bibliográficos
Autor(a) principal: Oliveira, Ana C. A. X. de
Data de Publicação: 2015
Outros Autores: Poça, Kátia S., Totino, Paulo R. R., Paumgartten, Francisco J.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/13846
Resumo: Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sérgio Arouca. Departamento de Ciências Biológicas. Laboratório de Toxicologia Ambiental. Rio de Janeiro, RJ, Brasil.
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spelling Oliveira, Ana C. A. X. dePoça, Kátia S.Totino, Paulo R. R.Paumgartten, Francisco J.2016-04-18T14:46:01Z2016-04-18T14:46:01Z2015OLIVEIRA, Ana C. A. X.de; Modulation of Cytochrome P450 2A5 Activity by Lipopolysaccharide: Low-Dose Effects and Non-Monotonic Dose-Response Relationship. Plos One, v.10, n.1, 15p, Jan. 2015.1932-6203https://www.arca.fiocruz.br/handle/icict/1384610.1371/journal.pone.0117842engPublic Library of ScienceCytochrome P450 2A5LipopolysaccharideMiceDose-Response Relationship, DrugMedicamentosCamundongosRelação Dose-Resposta a DrogaModulation of Cytochrome P450 2A5 Activity by Lipopolysaccharide: Low-Dose Effects and Non-Monotonic Dose-Response Relationshipinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sérgio Arouca. Departamento de Ciências Biológicas. Laboratório de Toxicologia Ambiental. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sérgio Arouca. Departamento de Ciências Biológicas. Laboratório de Toxicologia Ambiental. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Malária. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sérgio Arouca. Departamento de Ciências Biológicas. Laboratório de Toxicologia Ambiental. Rio de Janeiro, RJ, Brasil.Mouse cytochrome P450 (CYP) 2A5 is induced by inflammatory conditions and infectious diseases that down-regulate the expression and activity of most other CYP isoforms. Enhanced oxidative stress and nuclear factor (erythroid 2-related factor) 2 (Nrf2) transcription factor activation have been hypothesised to mediate up-regulation of CYP2A5 expression in the murine liver. The unique and complex regulation of CYP2A5, however, is far from being thoroughly elucidated. Sepsis and high doses of bacterial lipopolysaccharide (LPS) elicit oxidative stress in the liver, but depression, not induction, of CYP2A5 has been observed in studies of mice treated with LPS. The foregoing facts prompted us to evaluate the response of CYP2A5 liver activity in female DBA-2 mice over a broad range of LPS doses (0, 0.025, 0.05, 0.1, 0.2, 0.5, 1, 2, 5, 10, and 20 mg/kg). Cytokine levels (interleukin [IL]-2, IL-4, IL-6, IL-10, IL-17A, interferon gamma, tumour necrosis factor alpha) and nitric oxide (NO) were measured in the blood serum. Activities of CYP1A (EROD) and CYP2B (BROD) in the liver were also determined for comparative purposes. LPS depressed CYP2A5 at low doses (0.025–2.0 mg/kg) but not at doses (>2 mg/kg) that increased pro-inflammatory cytokines and NO serum levels, and depressed CYP1A and CYP2B activities. Blockade of proinflammatory cytokines and the overproduction of NO induced by co-treatment with pentoxifylline and LPS and iNOS inhibition with aminoguanidine both extended down-regulation of CYP2A5 to the high dose range while not affecting LPS-induced depression of CYP1A and CYP2B. Overall, the results suggested that NO plays a role in the reversal of the low-dose LPS-induced depression of CYP2A5 observed when mice were challenged with higher doses of LPS.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/13846/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALpaulo_totino_etal_IOC-2015.pdfpaulo_totino_etal_IOC-2015.pdfapplication/pdf779725https://www.arca.fiocruz.br/bitstream/icict/13846/2/paulo_totino_etal_IOC-2015.pdf9034bf229a28ea9c75c5b2b112abb346MD52TEXTpaulo_totino_etal_IOC-2015.pdf.txtpaulo_totino_etal_IOC-2015.pdf.txtExtracted texttext/plain45932https://www.arca.fiocruz.br/bitstream/icict/13846/3/paulo_totino_etal_IOC-2015.pdf.txt6a218676fa63fdd9f10bfbcf70612b45MD53icict/138462023-09-14 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dc.title.pt_BR.fl_str_mv Modulation of Cytochrome P450 2A5 Activity by Lipopolysaccharide: Low-Dose Effects and Non-Monotonic Dose-Response Relationship
title Modulation of Cytochrome P450 2A5 Activity by Lipopolysaccharide: Low-Dose Effects and Non-Monotonic Dose-Response Relationship
spellingShingle Modulation of Cytochrome P450 2A5 Activity by Lipopolysaccharide: Low-Dose Effects and Non-Monotonic Dose-Response Relationship
Oliveira, Ana C. A. X. de
Cytochrome P450 2A5
Lipopolysaccharide
Mice
Dose-Response Relationship, Drug
Medicamentos
Camundongos
Relação Dose-Resposta a Droga
title_short Modulation of Cytochrome P450 2A5 Activity by Lipopolysaccharide: Low-Dose Effects and Non-Monotonic Dose-Response Relationship
title_full Modulation of Cytochrome P450 2A5 Activity by Lipopolysaccharide: Low-Dose Effects and Non-Monotonic Dose-Response Relationship
title_fullStr Modulation of Cytochrome P450 2A5 Activity by Lipopolysaccharide: Low-Dose Effects and Non-Monotonic Dose-Response Relationship
title_full_unstemmed Modulation of Cytochrome P450 2A5 Activity by Lipopolysaccharide: Low-Dose Effects and Non-Monotonic Dose-Response Relationship
title_sort Modulation of Cytochrome P450 2A5 Activity by Lipopolysaccharide: Low-Dose Effects and Non-Monotonic Dose-Response Relationship
author Oliveira, Ana C. A. X. de
author_facet Oliveira, Ana C. A. X. de
Poça, Kátia S.
Totino, Paulo R. R.
Paumgartten, Francisco J.
author_role author
author2 Poça, Kátia S.
Totino, Paulo R. R.
Paumgartten, Francisco J.
author2_role author
author
author
dc.contributor.author.fl_str_mv Oliveira, Ana C. A. X. de
Poça, Kátia S.
Totino, Paulo R. R.
Paumgartten, Francisco J.
dc.subject.other.pt_BR.fl_str_mv Cytochrome P450 2A5
Lipopolysaccharide
Mice
Dose-Response Relationship, Drug
topic Cytochrome P450 2A5
Lipopolysaccharide
Mice
Dose-Response Relationship, Drug
Medicamentos
Camundongos
Relação Dose-Resposta a Droga
dc.subject.decs.pt_BR.fl_str_mv Medicamentos
Camundongos
Relação Dose-Resposta a Droga
description Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sérgio Arouca. Departamento de Ciências Biológicas. Laboratório de Toxicologia Ambiental. Rio de Janeiro, RJ, Brasil.
publishDate 2015
dc.date.issued.fl_str_mv 2015
dc.date.accessioned.fl_str_mv 2016-04-18T14:46:01Z
dc.date.available.fl_str_mv 2016-04-18T14:46:01Z
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, Ana C. A. X.de; Modulation of Cytochrome P450 2A5 Activity by Lipopolysaccharide: Low-Dose Effects and Non-Monotonic Dose-Response Relationship. Plos One, v.10, n.1, 15p, Jan. 2015.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/13846
dc.identifier.issn.none.fl_str_mv 1932-6203
dc.identifier.doi.none.fl_str_mv 10.1371/journal.pone.0117842
identifier_str_mv OLIVEIRA, Ana C. A. X.de; Modulation of Cytochrome P450 2A5 Activity by Lipopolysaccharide: Low-Dose Effects and Non-Monotonic Dose-Response Relationship. Plos One, v.10, n.1, 15p, Jan. 2015.
1932-6203
10.1371/journal.pone.0117842
url https://www.arca.fiocruz.br/handle/icict/13846
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)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/13846/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/13846/2/paulo_totino_etal_IOC-2015.pdf
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