Potencial terapêutico de um heparinóide isolado do invertebrado marinho Litopenaeus vannamei
Autor(a) principal: | |
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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 |
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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 |
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por |
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por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal do Rio Grande do Norte |
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Programa de Pós-Graduação em Bioquímica |
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UFRN |
dc.publisher.country.fl_str_mv |
BR |
dc.publisher.department.fl_str_mv |
Bioquímica; Biologia Molecular |
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Universidade Federal do Rio Grande do Norte |
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reponame:Repositório Institucional da UFRN instname:Universidade Federal do Rio Grande do Norte (UFRN) instacron:UFRN |
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