Efeito inibidor de leucotrieno (MK 0476) em modelo experimental da Síndromedo Desconforto Respiratório Agudo (SDRA) induzida por Lipopolissacarídeo (LPS)
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da Uninove |
Texto Completo: | http://bibliotecatede.uninove.br/handle/tede/3313 |
Resumo: | The acute respiratory distress syndrome (ARDS) has high mortality rates and may be the result both of lung infections such as extra pulmonary being characterized by respiratory failure from the inflammatory response that leads to alteration of alveolar-capillary permeability, edema and hypoxemia refractory to high flows oxygen. One of the most important mechanisms that determine the severity of this injury is the magnitude of the alveolar epithelial barrier injury. The possibility of epithelial repair at an early stage is the major determinant of recovery. Many of the therapeutic approaches in attempts to permeate decreased pulmonary inflammation to minimize the initial injury, which is largely due to the inflammatory process mediated by local and systemic activation by cytokines such as TNF-α and IL-8. In this sense, we aimed to evaluate the effects of leukotriene inhibitor (MK0476) on pulmonary and systemic inflammation. For this purpose, C57BL / 6 mice (n = 35) adults male were distributed into five groups: (1) Control 24 hours (n = 7; unhandled), (2) Control 48 hours (n = 7; unhandled) (3) Control IT LPS 24 hours (n = 7; intratracheal LPS; 10 mg / mouse) (4) Control IT LPS 48 hours (n = 7; intratracheal LPS; 10 mg / mouse), (5) IT + LPS MK0476 (n = 7; intratracheal LPS; 10mg / mouse + MK0476) .The animals were euthanized twenty-four hours after the LPS administration and evaluated the total cell and differential count in broncho alveolar lavage (BAL) protein levels in total BAL cytokine levels (IL-6, CXCL-1 / KC, IL-10, IL-17 and TNF-α) in serum and BAL supernatant and the density of neutrophils, lymphocytes and macrophages in the lung parenchyma. They also assessed the levels of VEGF in lung homogenate, and the expression of NF-kB and LTB4R leukocytes in the pulmonary parenchyma through imunohistochemistry. Moreover, IL-8 levels in the supernatant of human neutrophils stimulated in vitro with LPS (1.5 ug / ml of medium) and treated with MK0476 (10uM) was also evaluated. The results showed that the MK0476 is capable of decreasing the number of total cells (p <0.05), macrophages (p <0.05), neutrophils (p <0.01) and lymphocytes (p <0.001) in BAL, in addition to total protein levels (p <0.05), IL-6 (p <0.05) CXCL1 / KC (P <0.05), IL-17 (p <0.05) and TNF-α (p <0.05). The density of neutrophils (p <0.001), lymphocytes (p <0.001) and macrophage (p <0.01) in the lung parenchyma was also reduced by treatment with the MK0476. VEGF levels in lung homogenate (p <0.01) were re-established by treatment with the MK0476. Finally, treatment with the MK0476 is capable of reducing the expression of NF-kB and LTB4R leukocytes in the pulmonary parenchyma, suggesting a possible mechanism of action of MK0476 in acute lung inflammation induced by LPS. We therefore conclude that the MK0476, the model used, presents significant improvement in the levels of total proteins and cytokines, improving both systemic levels and local. |
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Vieira, Rodolfo de Paulahttp://lattes.cnpq.br/9213556008468472Consolim-Colombo, Fernanda Marcianohttp://lattes.cnpq.br/8102854014364848Vieira, Rodolfo de Paulahttp://lattes.cnpq.br/9213556008468472Romanholo, Beatriz Mangueira Saraivahttp://lattes.cnpq.br/6037246361594215Oliveira, Ana Paula Ligeiro dehttp://lattes.cnpq.br/5700855351581023http://lattes.cnpq.br/1957089096579382Chiovatto, Jaime Eduardo Davino2024-04-08T20:51:13Z2015-08-28Chiovatto, Jaime Eduardo Davino. Efeito inibidor de leucotrieno (MK 0476) em modelo experimental da Síndromedo Desconforto Respiratório Agudo (SDRA) induzida por Lipopolissacarídeo (LPS). 2015. 100 f. Dissertação( Programa de Mestrado em Medicina) - Universidade Nove de Julho, São Paulo.http://bibliotecatede.uninove.br/handle/tede/3313The acute respiratory distress syndrome (ARDS) has high mortality rates and may be the result both of lung infections such as extra pulmonary being characterized by respiratory failure from the inflammatory response that leads to alteration of alveolar-capillary permeability, edema and hypoxemia refractory to high flows oxygen. One of the most important mechanisms that determine the severity of this injury is the magnitude of the alveolar epithelial barrier injury. The possibility of epithelial repair at an early stage is the major determinant of recovery. Many of the therapeutic approaches in attempts to permeate decreased pulmonary inflammation to minimize the initial injury, which is largely due to the inflammatory process mediated by local and systemic activation by cytokines such as TNF-α and IL-8. In this sense, we aimed to evaluate the effects of leukotriene inhibitor (MK0476) on pulmonary and systemic inflammation. For this purpose, C57BL / 6 mice (n = 35) adults male were distributed into five groups: (1) Control 24 hours (n = 7; unhandled), (2) Control 48 hours (n = 7; unhandled) (3) Control IT LPS 24 hours (n = 7; intratracheal LPS; 10 mg / mouse) (4) Control IT LPS 48 hours (n = 7; intratracheal LPS; 10 mg / mouse), (5) IT + LPS MK0476 (n = 7; intratracheal LPS; 10mg / mouse + MK0476) .The animals were euthanized twenty-four hours after the LPS administration and evaluated the total cell and differential count in broncho alveolar lavage (BAL) protein levels in total BAL cytokine levels (IL-6, CXCL-1 / KC, IL-10, IL-17 and TNF-α) in serum and BAL supernatant and the density of neutrophils, lymphocytes and macrophages in the lung parenchyma. They also assessed the levels of VEGF in lung homogenate, and the expression of NF-kB and LTB4R leukocytes in the pulmonary parenchyma through imunohistochemistry. Moreover, IL-8 levels in the supernatant of human neutrophils stimulated in vitro with LPS (1.5 ug / ml of medium) and treated with MK0476 (10uM) was also evaluated. The results showed that the MK0476 is capable of decreasing the number of total cells (p <0.05), macrophages (p <0.05), neutrophils (p <0.01) and lymphocytes (p <0.001) in BAL, in addition to total protein levels (p <0.05), IL-6 (p <0.05) CXCL1 / KC (P <0.05), IL-17 (p <0.05) and TNF-α (p <0.05). The density of neutrophils (p <0.001), lymphocytes (p <0.001) and macrophage (p <0.01) in the lung parenchyma was also reduced by treatment with the MK0476. VEGF levels in lung homogenate (p <0.01) were re-established by treatment with the MK0476. Finally, treatment with the MK0476 is capable of reducing the expression of NF-kB and LTB4R leukocytes in the pulmonary parenchyma, suggesting a possible mechanism of action of MK0476 in acute lung inflammation induced by LPS. We therefore conclude that the MK0476, the model used, presents significant improvement in the levels of total proteins and cytokines, improving both systemic levels and local.A síndrome do desconforto respiratório agudo (SDRA) apresenta altas taxas de mortalidade, podendo ser resultante tanto de infecções pulmonares como extrapulmonares sendo caracterizada pela insuficiência respiratória proveniente da resposta inflamatória que cursa com alteração de permeabilidade alvéolo-capilar, edema e hipoxemia refratária aos altos fluxos de oxigênio. Um dos mais importantes mecanismos que determinam a severidade desta injúria é a magnitude da lesão da barreira epitélio alveolar. A possibilidade de reparação do epitélio em um estágio precoce é o maior determinante da recuperação. Muitas das modalidades terapêuticas permeiam na tentativa de diminuição da inflamação pulmonar para minimizar a lesão inicial, a qual se deve em grande parte ao processo inflamatório mediado pela ativação local e sistêmica de citocinas como TNF-α e IL-8. Nesse sentido, pretendemos avaliar os efeitos do inibidor de leucotrienos (MK0476) na inflamação pulmonar e sistêmica. Para isso, camundongos C57Bl/6 (n=35) adultos machos foram distribuídos em 5 grupos: Controle 24 horas (n=7; não manipulado), Controle 48 horas (n=7; não manipulado), LPS IT Controle 24 horas (n=7; LPS intratraqueal; 10 µg/camundongo), LPS IT Controle 48 horas (n=7; LPS intratraqueal; 10 µg/camundongo), LPS IT + MK0476 (n=7; LPS intratraqueal; 10µg/camundongo + MK0476).Os animais foram eutanasiados vinte e quatro horas após a administração de LPS e MK0476 sendo avaliada a contagem de células totais, diferenciais e os níveis de proteínas totais no lavado bronco alveolar (LBA), já os níveis de citocinas (IL-6, CXCL-1/KC, IL 10, IL-17 e TNF-α) dosados no soro e no sobrenadante do LBA e a densidade de neutrófilos, linfócitos e macrófagos no parênquima pulmonar. Foram avaliados ainda os níveis de VEGF no homogenato pulmonar, e a expressão do NF-kB e do LTB4R pelos leucócitos no parênquima pulmonar através de imunohistoquímica. Além disso, os níveis de IL-8 no sobrenadante dos neutrófilos de humanos estimulados in vitro com LPS (1,5 ug/ml de meio) e tratados com MK0476 (10uM) também foi avaliado. Os resultados demonstraram que o MK0476 foi capaz de diminuir o número de células totais (p<0.05), macrófagos (p<0.05), neutrófilos (p<0.01) e linfócitos (p<0.001) no LBA, além dos níveis de proteínas totais (p<0.05), IL-6 (p<0.05), CXCL1/KC (p<0.05), IL-17 (p<0.05) e TNF-α (p<0.05). A densidade de neutrófilos (p<0.001), linfócitos (p<0.001) e macrófagos (p<0.01) no parênquima pulmonar também foi diminuída através do tratamento com o MK0476. Os níveis de VEGF no homogenato pulmonar (p<0.01) foram reestabelecidos pelo tratamento com o MK0476. Por fim, o tratamento com o MK0476 foi capaz de reduzir a expressão de NF-kB e de LTB4R pelos leucócitos no parênquima pulmonar, sugerindo um possível mecanismo de ação do MK0476 na inflamação pulmonar aguda induzida por LPS. Portanto, concluímos que o MK0476, no modelo utilizado, apresenta significante melhora nos níveis de proteínas totais e citocinas, melhorando tanto os níveis sistêmicos quanto local.Submitted by Nadir Basilio (nadirsb@uninove.br) on 2024-04-08T20:51:13Z No. of bitstreams: 1 Jaime Eduardo Davino Chiovatto.pdf: 2410799 bytes, checksum: e3741cb17ce89b41593f21e2c2cdf3bb (MD5)Made available in DSpace on 2024-04-08T20:51:13Z (GMT). No. of bitstreams: 1 Jaime Eduardo Davino Chiovatto.pdf: 2410799 bytes, checksum: e3741cb17ce89b41593f21e2c2cdf3bb (MD5) Previous issue date: 2015-08-28application/pdfporUniversidade Nove de JulhoPrograma de Mestrado em MedicinaUNINOVEBrasilSaúdeinflamação pulmonarSDRAMK0476lung inflammationARDSMK0476CIENCIAS DA SAUDEEfeito inibidor de leucotrieno (MK 0476) em modelo experimental da Síndromedo Desconforto Respiratório Agudo (SDRA) induzida por Lipopolissacarídeo (LPS)Effects of leukotriene inhibitor (MK 0476) in a experimental model of Acute Respiratory Distress Syndrome (ARDS) induced by Lipopolysaccharide (LPS)info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis8765449414823306929600info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da Uninoveinstname:Universidade Nove de Julho (UNINOVE)instacron:UNINOVEORIGINALJaime Eduardo Davino Chiovatto.pdfJaime Eduardo Davino Chiovatto.pdfapplication/pdf2410799http://localhost:8080/tede/bitstream/tede/3313/2/Jaime+Eduardo+Davino+Chiovatto.pdfe3741cb17ce89b41593f21e2c2cdf3bbMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82165http://localhost:8080/tede/bitstream/tede/3313/1/license.txtbd3efa91386c1718a7f26a329fdcb468MD51tede/33132024-04-08 17:51:13.797oai:localhost: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Biblioteca Digital de Teses e Dissertaçõeshttp://bibliotecatede.uninove.br/PRIhttp://bibliotecatede.uninove.br/oai/requestbibliotecatede@uninove.br||bibliotecatede@uninove.bropendoar:2024-04-08T20:51:13Biblioteca Digital de Teses e Dissertações da Uninove - Universidade Nove de Julho (UNINOVE)false |
dc.title.por.fl_str_mv |
Efeito inibidor de leucotrieno (MK 0476) em modelo experimental da Síndromedo Desconforto Respiratório Agudo (SDRA) induzida por Lipopolissacarídeo (LPS) |
dc.title.alternative.eng.fl_str_mv |
Effects of leukotriene inhibitor (MK 0476) in a experimental model of Acute Respiratory Distress Syndrome (ARDS) induced by Lipopolysaccharide (LPS) |
title |
Efeito inibidor de leucotrieno (MK 0476) em modelo experimental da Síndromedo Desconforto Respiratório Agudo (SDRA) induzida por Lipopolissacarídeo (LPS) |
spellingShingle |
Efeito inibidor de leucotrieno (MK 0476) em modelo experimental da Síndromedo Desconforto Respiratório Agudo (SDRA) induzida por Lipopolissacarídeo (LPS) Chiovatto, Jaime Eduardo Davino inflamação pulmonar SDRA MK0476 lung inflammation ARDS MK0476 CIENCIAS DA SAUDE |
title_short |
Efeito inibidor de leucotrieno (MK 0476) em modelo experimental da Síndromedo Desconforto Respiratório Agudo (SDRA) induzida por Lipopolissacarídeo (LPS) |
title_full |
Efeito inibidor de leucotrieno (MK 0476) em modelo experimental da Síndromedo Desconforto Respiratório Agudo (SDRA) induzida por Lipopolissacarídeo (LPS) |
title_fullStr |
Efeito inibidor de leucotrieno (MK 0476) em modelo experimental da Síndromedo Desconforto Respiratório Agudo (SDRA) induzida por Lipopolissacarídeo (LPS) |
title_full_unstemmed |
Efeito inibidor de leucotrieno (MK 0476) em modelo experimental da Síndromedo Desconforto Respiratório Agudo (SDRA) induzida por Lipopolissacarídeo (LPS) |
title_sort |
Efeito inibidor de leucotrieno (MK 0476) em modelo experimental da Síndromedo Desconforto Respiratório Agudo (SDRA) induzida por Lipopolissacarídeo (LPS) |
author |
Chiovatto, Jaime Eduardo Davino |
author_facet |
Chiovatto, Jaime Eduardo Davino |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Vieira, Rodolfo de Paula |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/9213556008468472 |
dc.contributor.advisor-co1.fl_str_mv |
Consolim-Colombo, Fernanda Marciano |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/8102854014364848 |
dc.contributor.referee1.fl_str_mv |
Vieira, Rodolfo de Paula |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/9213556008468472 |
dc.contributor.referee2.fl_str_mv |
Romanholo, Beatriz Mangueira Saraiva |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/6037246361594215 |
dc.contributor.referee3.fl_str_mv |
Oliveira, Ana Paula Ligeiro de |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/5700855351581023 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/1957089096579382 |
dc.contributor.author.fl_str_mv |
Chiovatto, Jaime Eduardo Davino |
contributor_str_mv |
Vieira, Rodolfo de Paula Consolim-Colombo, Fernanda Marciano Vieira, Rodolfo de Paula Romanholo, Beatriz Mangueira Saraiva Oliveira, Ana Paula Ligeiro de |
dc.subject.por.fl_str_mv |
inflamação pulmonar SDRA MK0476 |
topic |
inflamação pulmonar SDRA MK0476 lung inflammation ARDS MK0476 CIENCIAS DA SAUDE |
dc.subject.eng.fl_str_mv |
lung inflammation ARDS MK0476 |
dc.subject.cnpq.fl_str_mv |
CIENCIAS DA SAUDE |
description |
The acute respiratory distress syndrome (ARDS) has high mortality rates and may be the result both of lung infections such as extra pulmonary being characterized by respiratory failure from the inflammatory response that leads to alteration of alveolar-capillary permeability, edema and hypoxemia refractory to high flows oxygen. One of the most important mechanisms that determine the severity of this injury is the magnitude of the alveolar epithelial barrier injury. The possibility of epithelial repair at an early stage is the major determinant of recovery. Many of the therapeutic approaches in attempts to permeate decreased pulmonary inflammation to minimize the initial injury, which is largely due to the inflammatory process mediated by local and systemic activation by cytokines such as TNF-α and IL-8. In this sense, we aimed to evaluate the effects of leukotriene inhibitor (MK0476) on pulmonary and systemic inflammation. For this purpose, C57BL / 6 mice (n = 35) adults male were distributed into five groups: (1) Control 24 hours (n = 7; unhandled), (2) Control 48 hours (n = 7; unhandled) (3) Control IT LPS 24 hours (n = 7; intratracheal LPS; 10 mg / mouse) (4) Control IT LPS 48 hours (n = 7; intratracheal LPS; 10 mg / mouse), (5) IT + LPS MK0476 (n = 7; intratracheal LPS; 10mg / mouse + MK0476) .The animals were euthanized twenty-four hours after the LPS administration and evaluated the total cell and differential count in broncho alveolar lavage (BAL) protein levels in total BAL cytokine levels (IL-6, CXCL-1 / KC, IL-10, IL-17 and TNF-α) in serum and BAL supernatant and the density of neutrophils, lymphocytes and macrophages in the lung parenchyma. They also assessed the levels of VEGF in lung homogenate, and the expression of NF-kB and LTB4R leukocytes in the pulmonary parenchyma through imunohistochemistry. Moreover, IL-8 levels in the supernatant of human neutrophils stimulated in vitro with LPS (1.5 ug / ml of medium) and treated with MK0476 (10uM) was also evaluated. The results showed that the MK0476 is capable of decreasing the number of total cells (p <0.05), macrophages (p <0.05), neutrophils (p <0.01) and lymphocytes (p <0.001) in BAL, in addition to total protein levels (p <0.05), IL-6 (p <0.05) CXCL1 / KC (P <0.05), IL-17 (p <0.05) and TNF-α (p <0.05). The density of neutrophils (p <0.001), lymphocytes (p <0.001) and macrophage (p <0.01) in the lung parenchyma was also reduced by treatment with the MK0476. VEGF levels in lung homogenate (p <0.01) were re-established by treatment with the MK0476. Finally, treatment with the MK0476 is capable of reducing the expression of NF-kB and LTB4R leukocytes in the pulmonary parenchyma, suggesting a possible mechanism of action of MK0476 in acute lung inflammation induced by LPS. We therefore conclude that the MK0476, the model used, presents significant improvement in the levels of total proteins and cytokines, improving both systemic levels and local. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-08-28 |
dc.date.accessioned.fl_str_mv |
2024-04-08T20:51:13Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Chiovatto, Jaime Eduardo Davino. Efeito inibidor de leucotrieno (MK 0476) em modelo experimental da Síndromedo Desconforto Respiratório Agudo (SDRA) induzida por Lipopolissacarídeo (LPS). 2015. 100 f. Dissertação( Programa de Mestrado em Medicina) - Universidade Nove de Julho, São Paulo. |
dc.identifier.uri.fl_str_mv |
http://bibliotecatede.uninove.br/handle/tede/3313 |
identifier_str_mv |
Chiovatto, Jaime Eduardo Davino. Efeito inibidor de leucotrieno (MK 0476) em modelo experimental da Síndromedo Desconforto Respiratório Agudo (SDRA) induzida por Lipopolissacarídeo (LPS). 2015. 100 f. Dissertação( Programa de Mestrado em Medicina) - Universidade Nove de Julho, São Paulo. |
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http://bibliotecatede.uninove.br/handle/tede/3313 |
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Universidade Nove de Julho |
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Programa de Mestrado em Medicina |
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UNINOVE |
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Brasil |
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Saúde |
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Universidade Nove de Julho |
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Biblioteca Digital de Teses e Dissertações da Uninove |
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Biblioteca Digital de Teses e Dissertações da Uninove |
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Biblioteca Digital de Teses e Dissertações da Uninove - Universidade Nove de Julho (UNINOVE) |
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bibliotecatede@uninove.br||bibliotecatede@uninove.br |
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