A????o da sinvastatina sobre o di??metro alveolar e a leucometria no l??quido broncoalveolar de ratos em modelo de enfisema elastase-induzido

Detalhes bibliográficos
Autor(a) principal: Jacobsen, Osneri
Data de Publicação: 2009
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da Uninove
Texto Completo: http://bibliotecatede.uninove.br/tede/handle/tede/820
Resumo: Pulmonary emphysema is characterized by reduction of lung parenchyma, which causes irreversible enlargement of the alveoli. It is, associated with chronic bronchitis, a manifestation of chronic obstructive pulmonary disease. Several mechanisms are involved in its development; presence of inflammatory cells into the lungs, imbalance between proteolytic and anti-proteolytic activity, apoptosis and oxidative stress. So far no therapy significantly reduces the inflammation and degeneration of emphysema. Simvastatin, an inhibitor of the enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, used as hypocholesterolemic, has shown anti-inflammatory and antioxidant activity in recent studies that could reduce the deleterious effects of chronic inflammation related to emphysema. This study evaluated the effect of simvastatin on leukometry and pulmonary alveolar diameter involved in the development of elastase-induced emphysema in rats. Were used 24 male rats divided into 4 groups (n=6): control (C), emphysema (E), emphysema treated with simvastatin (ES) and group without emphysema treated with simvastatin (S). The ES and S groups received simvastatin (10 mg/kg), C and E received vehicle (CMC 0.2%) for 28 continuous days in single daily doses, by gavage. The animals were sacrificed and the biological samples collected at 28?? day after initiation of treatment. Were quantified the number of leukocytes in bronchoalveolar fluid and the alveolar diameter of lung tissue. We also evaluated the direct inhibition of simvastatin over elastase and quantified the serum creatinekinase to evaluate the toxicity of the drug. The results showed that the 2 groups treated with simvastatin (S and ES) showed significant reduction of the leukocyte count (p <0.01) when compared to groups C and E. The evaluation of lung tissue, showed a significant increase in mean linear intercept (LM) of the emphysematous group compared to the control group and emphysema treated with simvastatin. The simvastatin is not a good inhibitor of elastase and did not induce toxicity in the dosage used. The results suggest that simvastatin reduces the inflammatory process involved in emphysema.
id NOVE_b853726efd8e9c995efe74aaf4bacddd
oai_identifier_str oai:localhost:tede/820
network_acronym_str NOVE
network_name_str Biblioteca Digital de Teses e Dissertações da Uninove
repository_id_str
spelling Nascimento, Jorge Willian Leandrohttp://lattes.cnpq.br/7576040220091720Costa, Maricilia Silvahttp://lattes.cnpq.br/7963390052508784Silva, Carlos AlbertoCPF:00000000000CPF:08710100000http://lattes.cnpq.br/0581031424154734Jacobsen, Osneri2015-04-22T17:20:24Z2010-04-292009-12-15JACOBSEN, Osneri. Action of the sinvastatin on the alveolar diameter and the leucometria in the liquid to broncoalveolar of rats in elastase-induced model of enfisema.. 2009. 69 f. Disserta????o (Mestrado em Sa??de) - Universidade Nove de Julho, S??o Paulo, 2009.http://bibliotecatede.uninove.br/tede/handle/tede/820Pulmonary emphysema is characterized by reduction of lung parenchyma, which causes irreversible enlargement of the alveoli. It is, associated with chronic bronchitis, a manifestation of chronic obstructive pulmonary disease. Several mechanisms are involved in its development; presence of inflammatory cells into the lungs, imbalance between proteolytic and anti-proteolytic activity, apoptosis and oxidative stress. So far no therapy significantly reduces the inflammation and degeneration of emphysema. Simvastatin, an inhibitor of the enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, used as hypocholesterolemic, has shown anti-inflammatory and antioxidant activity in recent studies that could reduce the deleterious effects of chronic inflammation related to emphysema. This study evaluated the effect of simvastatin on leukometry and pulmonary alveolar diameter involved in the development of elastase-induced emphysema in rats. Were used 24 male rats divided into 4 groups (n=6): control (C), emphysema (E), emphysema treated with simvastatin (ES) and group without emphysema treated with simvastatin (S). The ES and S groups received simvastatin (10 mg/kg), C and E received vehicle (CMC 0.2%) for 28 continuous days in single daily doses, by gavage. The animals were sacrificed and the biological samples collected at 28?? day after initiation of treatment. Were quantified the number of leukocytes in bronchoalveolar fluid and the alveolar diameter of lung tissue. We also evaluated the direct inhibition of simvastatin over elastase and quantified the serum creatinekinase to evaluate the toxicity of the drug. The results showed that the 2 groups treated with simvastatin (S and ES) showed significant reduction of the leukocyte count (p <0.01) when compared to groups C and E. The evaluation of lung tissue, showed a significant increase in mean linear intercept (LM) of the emphysematous group compared to the control group and emphysema treated with simvastatin. The simvastatin is not a good inhibitor of elastase and did not induce toxicity in the dosage used. The results suggest that simvastatin reduces the inflammatory process involved in emphysema.O enfisema pulmonar ?? caracterizado por redu????o do par??nquima pulmonar, que ocasiona alargamento irrevers??vel dos alv??olos. Constitui, junto com a bronquite cr??nica, uma das manifesta????es da doen??a pulmonar obstrutiva cr??nica. Diversos mecanismos est??o envolvidos no desenvolvimento do enfisema como a presen??a de c??lulas inflamat??rias, desequil??brio proteinase/antiproteinase e elevado estresse oxidativo, que induzem o aumento da apoptose de c??lulas epiteliais e endoteliais alveolares. O processo apopt??tico aumentado no enfisema colabora para a destrui????o alveolar. At?? agora nenhuma terapia reduz significativamente o processo inflamat??rio e degenerativo do enfisema. A sinvastatina, um inibidor da enzima 3-hidroxi-3-metil-glutaril coenzime-A redutase, usada como hipocolesterol??mico, vem apresentando atividade antiinflamat??ria, antioxidante e reparadora que poderiam reduzir os efeitos delet??rios do processo inflamat??rio cr??nico ligado ao enfisema. Neste estudo avaliou-se o efeito da administra????o de sinvastatina sobre a leucometria no l??quido broncoalveolar (BALF) e o di??metro alveolar do tecido pulmonar (Lm) envolvido no desenvolvimento do enfisema elastase-induzido em ratos. Foram usados 24 ratos machos, divididos em 4 grupos (n=6): controle (C), enfisema (E), enfisema tratado com sinvastatina (ES) e grupo sem enfisema tratado com sinvastatina (S). Os grupos ES e S receberam sinvastatina (10 mg/kg) e C e E receberam o ve??culo (CMC 0.2%) por 28 dias consecutivos em doses ??nicas di??rias, por gavage. Os animais foram sacrificados e as amostras biol??gicas coletadas no 28?? dias ap??s in??cio do tratamento. Os resultados da contagem de leuc??citos no BALF mostraram redu????o significativa dos grupos tratados com sinvastatina em rela????o aos n??o tratados (p<0,01). No Lm observou-se aumento significativo do grupo Enfisema em rela????o aos grupos Controle e Sinvastatina. Foram avaliados os efeitos da sinvastatina sobre a atividade enzim??tica da elastase e quantificada a creatinofosfoquinase s??rica (CK) para avalia????o da toxicidade do f??rmaco. Os dados mostram que a sinvastatina n??o ?? um bom inibidor da elastase e que n??o induziu toxicidade na dosagem utilizada. Os resultados sugerem que a sinvastatina reduz o processo inflamat??rio envolvido no enfisema.Made available in DSpace on 2015-04-22T17:20:24Z (GMT). No. of bitstreams: 1 B_Osneri Jacobsen.pdf: 337222 bytes, checksum: d10d7083b7f76567be44a814fad8316d (MD5) Previous issue date: 2009-12-15application/pdfporUniversidade Nove de JulhoPrograma de P??s-Gradua????o em Ci??ncias da Reabilita????oUNINOVEBRSa??deenfisemaapoptosesinvastatinaleuc??citoelastaseemphysemasimvastatinleukocyteselastaseinflammationCIENCIAS DA SAUDEA????o da sinvastatina sobre o di??metro alveolar e a leucometria no l??quido broncoalveolar de ratos em modelo de enfisema elastase-induzidoAction of the sinvastatin on the alveolar diameter and the leucometria in the liquid to broncoalveolar of rats in elastase-induced model of enfisemainfo: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:UNINOVEORIGINALB_Osneri Jacobsen.pdfapplication/pdf337222http://localhost:8080/tede/bitstream/tede/820/1/B_Osneri+Jacobsen.pdfd10d7083b7f76567be44a814fad8316dMD51tede/8202018-06-15 12:46:07.389oai:localhost:tede/820Biblioteca Digital de Teses e Dissertaçõeshttp://bibliotecatede.uninove.br/PRIhttp://bibliotecatede.uninove.br/oai/requestbibliotecatede@uninove.br||bibliotecatede@uninove.bropendoar:2018-06-15T15:46:07Biblioteca Digital de Teses e Dissertações da Uninove - Universidade Nove de Julho (UNINOVE)false
dc.title.por.fl_str_mv A????o da sinvastatina sobre o di??metro alveolar e a leucometria no l??quido broncoalveolar de ratos em modelo de enfisema elastase-induzido
dc.title.alternative.eng.fl_str_mv Action of the sinvastatin on the alveolar diameter and the leucometria in the liquid to broncoalveolar of rats in elastase-induced model of enfisema
title A????o da sinvastatina sobre o di??metro alveolar e a leucometria no l??quido broncoalveolar de ratos em modelo de enfisema elastase-induzido
spellingShingle A????o da sinvastatina sobre o di??metro alveolar e a leucometria no l??quido broncoalveolar de ratos em modelo de enfisema elastase-induzido
Jacobsen, Osneri
enfisema
apoptose
sinvastatina
leuc??cito
elastase
emphysema
simvastatin
leukocytes
elastase
inflammation
CIENCIAS DA SAUDE
title_short A????o da sinvastatina sobre o di??metro alveolar e a leucometria no l??quido broncoalveolar de ratos em modelo de enfisema elastase-induzido
title_full A????o da sinvastatina sobre o di??metro alveolar e a leucometria no l??quido broncoalveolar de ratos em modelo de enfisema elastase-induzido
title_fullStr A????o da sinvastatina sobre o di??metro alveolar e a leucometria no l??quido broncoalveolar de ratos em modelo de enfisema elastase-induzido
title_full_unstemmed A????o da sinvastatina sobre o di??metro alveolar e a leucometria no l??quido broncoalveolar de ratos em modelo de enfisema elastase-induzido
title_sort A????o da sinvastatina sobre o di??metro alveolar e a leucometria no l??quido broncoalveolar de ratos em modelo de enfisema elastase-induzido
author Jacobsen, Osneri
author_facet Jacobsen, Osneri
author_role author
dc.contributor.advisor1.fl_str_mv Nascimento, Jorge Willian Leandro
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/7576040220091720
dc.contributor.referee1.fl_str_mv Costa, Maricilia Silva
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/7963390052508784
dc.contributor.referee2.fl_str_mv Silva, Carlos Alberto
dc.contributor.referee2ID.fl_str_mv CPF:00000000000
dc.contributor.authorID.fl_str_mv CPF:08710100000
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/0581031424154734
dc.contributor.author.fl_str_mv Jacobsen, Osneri
contributor_str_mv Nascimento, Jorge Willian Leandro
Costa, Maricilia Silva
Silva, Carlos Alberto
dc.subject.por.fl_str_mv enfisema
apoptose
sinvastatina
leuc??cito
elastase
topic enfisema
apoptose
sinvastatina
leuc??cito
elastase
emphysema
simvastatin
leukocytes
elastase
inflammation
CIENCIAS DA SAUDE
dc.subject.eng.fl_str_mv emphysema
simvastatin
leukocytes
elastase
inflammation
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE
description Pulmonary emphysema is characterized by reduction of lung parenchyma, which causes irreversible enlargement of the alveoli. It is, associated with chronic bronchitis, a manifestation of chronic obstructive pulmonary disease. Several mechanisms are involved in its development; presence of inflammatory cells into the lungs, imbalance between proteolytic and anti-proteolytic activity, apoptosis and oxidative stress. So far no therapy significantly reduces the inflammation and degeneration of emphysema. Simvastatin, an inhibitor of the enzyme 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, used as hypocholesterolemic, has shown anti-inflammatory and antioxidant activity in recent studies that could reduce the deleterious effects of chronic inflammation related to emphysema. This study evaluated the effect of simvastatin on leukometry and pulmonary alveolar diameter involved in the development of elastase-induced emphysema in rats. Were used 24 male rats divided into 4 groups (n=6): control (C), emphysema (E), emphysema treated with simvastatin (ES) and group without emphysema treated with simvastatin (S). The ES and S groups received simvastatin (10 mg/kg), C and E received vehicle (CMC 0.2%) for 28 continuous days in single daily doses, by gavage. The animals were sacrificed and the biological samples collected at 28?? day after initiation of treatment. Were quantified the number of leukocytes in bronchoalveolar fluid and the alveolar diameter of lung tissue. We also evaluated the direct inhibition of simvastatin over elastase and quantified the serum creatinekinase to evaluate the toxicity of the drug. The results showed that the 2 groups treated with simvastatin (S and ES) showed significant reduction of the leukocyte count (p <0.01) when compared to groups C and E. The evaluation of lung tissue, showed a significant increase in mean linear intercept (LM) of the emphysematous group compared to the control group and emphysema treated with simvastatin. The simvastatin is not a good inhibitor of elastase and did not induce toxicity in the dosage used. The results suggest that simvastatin reduces the inflammatory process involved in emphysema.
publishDate 2009
dc.date.issued.fl_str_mv 2009-12-15
dc.date.available.fl_str_mv 2010-04-29
dc.date.accessioned.fl_str_mv 2015-04-22T17:20:24Z
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 JACOBSEN, Osneri. Action of the sinvastatin on the alveolar diameter and the leucometria in the liquid to broncoalveolar of rats in elastase-induced model of enfisema.. 2009. 69 f. Disserta????o (Mestrado em Sa??de) - Universidade Nove de Julho, S??o Paulo, 2009.
dc.identifier.uri.fl_str_mv http://bibliotecatede.uninove.br/tede/handle/tede/820
identifier_str_mv JACOBSEN, Osneri. Action of the sinvastatin on the alveolar diameter and the leucometria in the liquid to broncoalveolar of rats in elastase-induced model of enfisema.. 2009. 69 f. Disserta????o (Mestrado em Sa??de) - Universidade Nove de Julho, S??o Paulo, 2009.
url http://bibliotecatede.uninove.br/tede/handle/tede/820
dc.language.iso.fl_str_mv por
language por
dc.relation.cnpq.fl_str_mv 8765449414823306929
dc.relation.confidence.fl_str_mv 600
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Nove de Julho
dc.publisher.program.fl_str_mv Programa de P??s-Gradua????o em Ci??ncias da Reabilita????o
dc.publisher.initials.fl_str_mv UNINOVE
dc.publisher.country.fl_str_mv BR
dc.publisher.department.fl_str_mv Sa??de
publisher.none.fl_str_mv Universidade Nove de Julho
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da Uninove
instname:Universidade Nove de Julho (UNINOVE)
instacron:UNINOVE
instname_str Universidade Nove de Julho (UNINOVE)
instacron_str UNINOVE
institution UNINOVE
reponame_str Biblioteca Digital de Teses e Dissertações da Uninove
collection Biblioteca Digital de Teses e Dissertações da Uninove
bitstream.url.fl_str_mv http://localhost:8080/tede/bitstream/tede/820/1/B_Osneri+Jacobsen.pdf
bitstream.checksum.fl_str_mv d10d7083b7f76567be44a814fad8316d
bitstream.checksumAlgorithm.fl_str_mv MD5
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da Uninove - Universidade Nove de Julho (UNINOVE)
repository.mail.fl_str_mv bibliotecatede@uninove.br||bibliotecatede@uninove.br
_version_ 1811016863108300800