Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei

Detalhes bibliográficos
Autor(a) principal: Brito, Adriana da Silva
Data de Publicação: 2008
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFRN
Texto Completo: https://repositorio.ufrn.br/jspui/handle/123456789/12521
Resumo: The occurrence of bioactive compounds in marine organisms comes awaking the interest of the pharmaceutical industry. Heparin, a sulfated polysaccharide which presence was already identified in several marine invertebrates, is very attractive due its remarkable functional versatility. Besides to intervene in blood coagulation, this molecule has a great anti-inflammatory potential. However, its strong anticoagulant activity difficult the clinical exploitation of its anti-inflammatory properties. Thus, the aims of this work were to evaluate the effect of a heparin-like compound (heparinoid), isolated from the cephalotorax of the Litopenaeus vannamei shrimp, on the inflammatory response, hemostasia and synthesis of antithrombotic heparan sulfate by endothelial cells, besides studying some aspects concerning its structure. The purified heparinoid was structurally characterized following an analytical boarding, involving electrophoresis and chromatography. The structural analysis have shown that this compound possess a high content of glucuronic acid residues and disulfated disaccharide units. In contrast to mammalian heparin, the heparinoid was incapable to stimulate the synthesis of heparan sulfate by endothelial cells in the tested concentrations, beyond to show reduced anticoagulant activity and hemorrhagic effect. In a model of acute inflammation, the compound isolated from the shrimp reduced more than 50% of the cellular infiltration. Besides reduce the activity of MMP-9 and proMMP-2 of the peritoneal lavage of inflamed animals, the heparinoid also reduced the activity of MMP-9 secreted by activated human leukocytes. These results demonstrate the potential of heparinoid from L. vannamei to intervene in the inflammatory response. For possessing reduced anticoagulant activity and hemorrhagic effect, this compound can serve as a structural model to direct the development of more specific therapeutical agents to the treatment of inflammatory diseases
id UFRN_d75de9c0de15762b77f45761f4d2d428
oai_identifier_str oai:https://repositorio.ufrn.br:123456789/12521
network_acronym_str UFRN
network_name_str Repositório Institucional da UFRN
repository_id_str
spelling Brito, Adriana da Silvahttp://lattes.cnpq.br/0887305061762326http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4786250T8Santos, Elizeu Antunes doshttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782221T9&dataRevisao=nullToma, Lenyhttp://lattes.cnpq.br/3669434753963813Oliveira, Fernanda Wanderley dehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4786179U0&dataRevisao=nullChavante, Suely Ferreira2014-12-17T14:03:25Z2008-07-282014-12-17T14:03:25Z2008-06-13BRITO, Adriana da Silva. Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei. 2008. 84 f. Dissertação (Mestrado em Bioquímica; Biologia Molecular) - Universidade Federal do Rio Grande do Norte, Natal, 2008.https://repositorio.ufrn.br/jspui/handle/123456789/12521The occurrence of bioactive compounds in marine organisms comes awaking the interest of the pharmaceutical industry. Heparin, a sulfated polysaccharide which presence was already identified in several marine invertebrates, is very attractive due its remarkable functional versatility. Besides to intervene in blood coagulation, this molecule has a great anti-inflammatory potential. However, its strong anticoagulant activity difficult the clinical exploitation of its anti-inflammatory properties. Thus, the aims of this work were to evaluate the effect of a heparin-like compound (heparinoid), isolated from the cephalotorax of the Litopenaeus vannamei shrimp, on the inflammatory response, hemostasia and synthesis of antithrombotic heparan sulfate by endothelial cells, besides studying some aspects concerning its structure. The purified heparinoid was structurally characterized following an analytical boarding, involving electrophoresis and chromatography. The structural analysis have shown that this compound possess a high content of glucuronic acid residues and disulfated disaccharide units. In contrast to mammalian heparin, the heparinoid was incapable to stimulate the synthesis of heparan sulfate by endothelial cells in the tested concentrations, beyond to show reduced anticoagulant activity and hemorrhagic effect. In a model of acute inflammation, the compound isolated from the shrimp reduced more than 50% of the cellular infiltration. Besides reduce the activity of MMP-9 and proMMP-2 of the peritoneal lavage of inflamed animals, the heparinoid also reduced the activity of MMP-9 secreted by activated human leukocytes. These results demonstrate the potential of heparinoid from L. vannamei to intervene in the inflammatory response. For possessing reduced anticoagulant activity and hemorrhagic effect, this compound can serve as a structural model to direct the development of more specific therapeutical agents to the treatment of inflammatory diseasesA ocorrência de compostos bioativos em representantes da biodiversidade marinha vem despertando o interesse da indústria farmacêutica. Heparina, um polissacarídeo sulfatado cuja presença já foi identificada em vários invertebrados marinhos, destaca-se por sua extraordinária versatilidade funcional. Além de interferir na coagulação sanguínea, essa molécula possui grande potencial antiinflamatório. No entanto, sua forte atividade anticoagulante dificulta o aproveitamento clínico de sua propriedade antiinflamatória, o que estimula a pesquisa por análogos de heparina com efeitos colaterais reduzidos. Diante disso, este trabalho teve por objetivos avaliar o efeito de um composto semelhante à heparina (heparinóide), isolado do cefalotórax do camarão Litopenaeus vannamei, sobre a resposta inflamatória, hemostasia e síntese de heparam sulfato antitrombótico pelas células endoteliais, além de estudar alguns aspectos relevantes a cerca de sua estrutura. O heparinóide purificado foi estruturalmente caracterizado seguindo uma abordagem analítica, envolvendo eletroforeses e cromatografias. As análises estruturais mostraram que esse composto possui um elevado conteúdo de resíduos de ácido glucurônico e de dissacarídeos dissulfatados. Ao contrário da heparina de mamíferos, o heparinóide foi incapaz de estimular a síntese de heparam sulfato pelas células endoteliais nas concentrações testadas, além de apresentar atividade anticoagulante in vitro e efeito hemorrágico reduzidos. Em um modelo de inflamação aguda, o composto isolado do camarão reduziu mais de 50% da infiltração celular. Além de reduzir a atividade de MMP-9 e proMMP-2 no lavado peritoneal dos animais submetidos ao modelo de inflamação, o heparinóide também reduziu a atividade de MMP-9 secretada por leucócitos humanos ativados. Esses resultados demonstram o potencial do heparinóide de L. vannamei em interferir em vários eventos da resposta inflamatória. Por possuir atividade anticoagulante e efeito hemorrágico reduzidos, esse composto pode servir como um modelo estrutural para direcionar o desenvolvimento de agentes terapêuticos mais específicos para o tratamento de doenças inflamatóriasCoordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal do Rio Grande do NortePrograma de Pós-Graduação em BioquímicaUFRNBRBioquímica; Biologia MolecularLitopenaeus vannameiCompostos bioativosHeparinaHeparinóideInflamaçãoLitopenaeus vannameiBioactive compoundsHeparinHeparinoidInflammationCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAPotencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannameiinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRNinstname:Universidade Federal do Rio Grande do Norte (UFRN)instacron:UFRNTEXTAdrianaSB.pdf.txtAdrianaSB.pdf.txtExtracted texttext/plain136296https://repositorio.ufrn.br/bitstream/123456789/12521/6/AdrianaSB.pdf.txt91561138e2245748ba2f56c03fd56ea7MD56PotencialTerapêuticoHeparinóide_Brito_2009.pdf.txtPotencialTerapêuticoHeparinóide_Brito_2009.pdf.txtExtracted texttext/plain136296https://repositorio.ufrn.br/bitstream/123456789/12521/8/PotencialTerap%c3%aauticoHeparin%c3%b3ide_Brito_2009.pdf.txt91561138e2245748ba2f56c03fd56ea7MD58PotencialTerapêuticoHeparinóide_Brito_2009.pdf.txtPotencialTerapêuticoHeparinóide_Brito_2009.pdf.txtExtracted texttext/plain136296https://repositorio.ufrn.br/bitstream/123456789/12521/8/PotencialTerap%c3%aauticoHeparin%c3%b3ide_Brito_2009.pdf.txt91561138e2245748ba2f56c03fd56ea7MD58THUMBNAILAdrianaSB.pdf.jpgAdrianaSB.pdf.jpgIM Thumbnailimage/jpeg3145https://repositorio.ufrn.br/bitstream/123456789/12521/7/AdrianaSB.pdf.jpgd2729203948b5bee13658b5dbc9d052aMD57PotencialTerapêuticoHeparinóide_Brito_2009.pdf.jpgPotencialTerapêuticoHeparinóide_Brito_2009.pdf.jpgIM Thumbnailimage/jpeg3145https://repositorio.ufrn.br/bitstream/123456789/12521/9/PotencialTerap%c3%aauticoHeparin%c3%b3ide_Brito_2009.pdf.jpgd2729203948b5bee13658b5dbc9d052aMD59PotencialTerapêuticoHeparinóide_Brito_2009.pdf.jpgPotencialTerapêuticoHeparinóide_Brito_2009.pdf.jpgIM Thumbnailimage/jpeg3145https://repositorio.ufrn.br/bitstream/123456789/12521/9/PotencialTerap%c3%aauticoHeparin%c3%b3ide_Brito_2009.pdf.jpgd2729203948b5bee13658b5dbc9d052aMD59ORIGINALPotencialTerapêuticoHeparinóide_Brito_2009.pdfapplication/pdf1664966https://repositorio.ufrn.br/bitstream/123456789/12521/1/PotencialTerap%c3%aauticoHeparin%c3%b3ide_Brito_2009.pdf33b28b577c6c69f20823f4e4a84e7540MD51123456789/125212019-01-30 03:48:57.519oai:https://repositorio.ufrn.br:123456789/12521Repositório de PublicaçõesPUBhttp://repositorio.ufrn.br/oai/opendoar:2019-01-30T06:48:57Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)false
dc.title.por.fl_str_mv Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei
title Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei
spellingShingle Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei
Brito, Adriana da Silva
Litopenaeus vannamei
Compostos bioativos
Heparina
Heparinóide
Inflamação
Litopenaeus vannamei
Bioactive compounds
Heparin
Heparinoid
Inflammation
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
title_short Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei
title_full Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei
title_fullStr Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei
title_full_unstemmed Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei
title_sort Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei
author Brito, Adriana da Silva
author_facet Brito, Adriana da Silva
author_role author
dc.contributor.authorID.por.fl_str_mv
dc.contributor.authorLattes.por.fl_str_mv http://lattes.cnpq.br/0887305061762326
dc.contributor.advisorID.por.fl_str_mv
dc.contributor.advisorLattes.por.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4786250T8
dc.contributor.advisor-co1ID.por.fl_str_mv
dc.contributor.referees1.pt_BR.fl_str_mv Toma, Leny
dc.contributor.referees1ID.por.fl_str_mv
dc.contributor.referees1Lattes.por.fl_str_mv http://lattes.cnpq.br/3669434753963813
dc.contributor.referees2.pt_BR.fl_str_mv Oliveira, Fernanda Wanderley de
dc.contributor.referees2ID.por.fl_str_mv
dc.contributor.referees2Lattes.por.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4786179U0&dataRevisao=null
dc.contributor.author.fl_str_mv Brito, Adriana da Silva
dc.contributor.advisor-co1.fl_str_mv Santos, Elizeu Antunes dos
dc.contributor.advisor-co1Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782221T9&dataRevisao=null
dc.contributor.advisor1.fl_str_mv Chavante, Suely Ferreira
contributor_str_mv Santos, Elizeu Antunes dos
Chavante, Suely Ferreira
dc.subject.por.fl_str_mv Litopenaeus vannamei
Compostos bioativos
Heparina
Heparinóide
Inflamação
topic Litopenaeus vannamei
Compostos bioativos
Heparina
Heparinóide
Inflamação
Litopenaeus vannamei
Bioactive compounds
Heparin
Heparinoid
Inflammation
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
dc.subject.eng.fl_str_mv Litopenaeus vannamei
Bioactive compounds
Heparin
Heparinoid
Inflammation
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
description The occurrence of bioactive compounds in marine organisms comes awaking the interest of the pharmaceutical industry. Heparin, a sulfated polysaccharide which presence was already identified in several marine invertebrates, is very attractive due its remarkable functional versatility. Besides to intervene in blood coagulation, this molecule has a great anti-inflammatory potential. However, its strong anticoagulant activity difficult the clinical exploitation of its anti-inflammatory properties. Thus, the aims of this work were to evaluate the effect of a heparin-like compound (heparinoid), isolated from the cephalotorax of the Litopenaeus vannamei shrimp, on the inflammatory response, hemostasia and synthesis of antithrombotic heparan sulfate by endothelial cells, besides studying some aspects concerning its structure. The purified heparinoid was structurally characterized following an analytical boarding, involving electrophoresis and chromatography. The structural analysis have shown that this compound possess a high content of glucuronic acid residues and disulfated disaccharide units. In contrast to mammalian heparin, the heparinoid was incapable to stimulate the synthesis of heparan sulfate by endothelial cells in the tested concentrations, beyond to show reduced anticoagulant activity and hemorrhagic effect. In a model of acute inflammation, the compound isolated from the shrimp reduced more than 50% of the cellular infiltration. Besides reduce the activity of MMP-9 and proMMP-2 of the peritoneal lavage of inflamed animals, the heparinoid also reduced the activity of MMP-9 secreted by activated human leukocytes. These results demonstrate the potential of heparinoid from L. vannamei to intervene in the inflammatory response. For possessing reduced anticoagulant activity and hemorrhagic effect, this compound can serve as a structural model to direct the development of more specific therapeutical agents to the treatment of inflammatory diseases
publishDate 2008
dc.date.available.fl_str_mv 2008-07-28
2014-12-17T14:03:25Z
dc.date.issued.fl_str_mv 2008-06-13
dc.date.accessioned.fl_str_mv 2014-12-17T14:03:25Z
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 BRITO, Adriana da Silva. Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei. 2008. 84 f. Dissertação (Mestrado em Bioquímica; Biologia Molecular) - Universidade Federal do Rio Grande do Norte, Natal, 2008.
dc.identifier.uri.fl_str_mv https://repositorio.ufrn.br/jspui/handle/123456789/12521
identifier_str_mv BRITO, Adriana da Silva. Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei. 2008. 84 f. Dissertação (Mestrado em Bioquímica; Biologia Molecular) - Universidade Federal do Rio Grande do Norte, Natal, 2008.
url https://repositorio.ufrn.br/jspui/handle/123456789/12521
dc.language.iso.fl_str_mv por
language por
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 Federal do Rio Grande do Norte
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Bioquímica
dc.publisher.initials.fl_str_mv UFRN
dc.publisher.country.fl_str_mv BR
dc.publisher.department.fl_str_mv Bioquímica; Biologia Molecular
publisher.none.fl_str_mv Universidade Federal do Rio Grande do Norte
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFRN
instname:Universidade Federal do Rio Grande do Norte (UFRN)
instacron:UFRN
instname_str Universidade Federal do Rio Grande do Norte (UFRN)
instacron_str UFRN
institution UFRN
reponame_str Repositório Institucional da UFRN
collection Repositório Institucional da UFRN
bitstream.url.fl_str_mv https://repositorio.ufrn.br/bitstream/123456789/12521/6/AdrianaSB.pdf.txt
https://repositorio.ufrn.br/bitstream/123456789/12521/8/PotencialTerap%c3%aauticoHeparin%c3%b3ide_Brito_2009.pdf.txt
https://repositorio.ufrn.br/bitstream/123456789/12521/8/PotencialTerap%c3%aauticoHeparin%c3%b3ide_Brito_2009.pdf.txt
https://repositorio.ufrn.br/bitstream/123456789/12521/7/AdrianaSB.pdf.jpg
https://repositorio.ufrn.br/bitstream/123456789/12521/9/PotencialTerap%c3%aauticoHeparin%c3%b3ide_Brito_2009.pdf.jpg
https://repositorio.ufrn.br/bitstream/123456789/12521/9/PotencialTerap%c3%aauticoHeparin%c3%b3ide_Brito_2009.pdf.jpg
https://repositorio.ufrn.br/bitstream/123456789/12521/1/PotencialTerap%c3%aauticoHeparin%c3%b3ide_Brito_2009.pdf
bitstream.checksum.fl_str_mv 91561138e2245748ba2f56c03fd56ea7
91561138e2245748ba2f56c03fd56ea7
91561138e2245748ba2f56c03fd56ea7
d2729203948b5bee13658b5dbc9d052a
d2729203948b5bee13658b5dbc9d052a
d2729203948b5bee13658b5dbc9d052a
33b28b577c6c69f20823f4e4a84e7540
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositório Institucional da UFRN - Universidade Federal do Rio Grande do Norte (UFRN)
repository.mail.fl_str_mv
_version_ 1802117685556805632