Potencial antitrombótico de hidrolisado ácido de polissacarídeos sulfatados de Hypnea musciformis (Wulfen) J.V. Lamouroux

Detalhes bibliográficos
Ano de defesa: 2020
Autor(a) principal: Peixoto, Caroline Landim
Orientador(a): Moreira, Renato de Azevedo
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/55506
Resumo: Venous thrombosis is the main cause of current morbidity and mortality. It is estimated that 2 / 1,000 individuals suffer from this disease. Antithrombotic drugs are commonly used as a prophylactic measure by those who are predisposed to thrombus formation. The most wellknown and used antithrombotics are Unfractionated Heparin (UFH) and Low Molecular Weight Heparin (LMWH), the second being obtained by depolymerizing the first. Because these drugs are produced in animals and have serious side effects such as hemorrhage, there is a demand for the discovery of new antithrombotic drugs of non-animal origin and with reduced side effects. It is known in the literature that sulfated polysaccharides from red marine algae have antithrombotic activity. This work aimed to evaluate the antithrombotic potential of the acid hydrolysis product of sulfated polysaccharides extracted from the red seaweed Hypnea musciformis (Wulfen) J.V. Lamouroux. A hydrolysis design was carried out to obtain sulfated galactans of different molecular weights. The molecular weight of the hydrolyzate was estimated by Gel Permeation Chromatography (GPC) and characterized by the presence of sulfation and functional groups characteristic by Infrared. Four samples of different molecular weights were selected to investigate their antithrombotic activity, the EX 1, 5 and 7 and the intact polysaccharide (PS-Hm). The in vitro antithrombotic activity was analyzed by the tests of partially activated thromboplastin time (APTT) and prothrombin time (TP), both using LMWH CLEXANE ® as a positive control. Only the intact PS-Hm and the EX 5 prolonged the clotting time in the APTT, and none of the analyzed samples influenced the TP. The bleeding time test was performed to assess the bleeding tendency with intact PS-Hm and EX 5, using LMWH CLEXANE ® as a positive control. The analyzed samples had no significant difference in relation to the negative control and both samples showed a hemorrhagic tendency much lower than the positive control. The results indicate that the antithrombotic and anticoagulant activity is related to the molecular weight of the sulfated polysaccharide, and that the reduction in molecular weight can reduce the hemorrhagic tendency. Such results suggest that the samples are candidates for new antithrombotic drugs, however more tests are needed to confirm the activity, such as the model of venous thrombosis in rats.
id UFC-7_c0d0a1d65d9ab50d00bb76acefd7460f
oai_identifier_str oai:repositorio.ufc.br:riufc/55506
network_acronym_str UFC-7
network_name_str Repositório Institucional da Universidade Federal do Ceará (UFC)
repository_id_str
spelling Peixoto, Caroline LandimMoreira, Renato de Azevedo2020-11-27T16:22:33Z2020-11-27T16:22:33Z2020PEIXOTO, Caroline Landim. Potencial antitrombótico de hidrolisado ácido de polissacarídeos sulfatados de Hypnea musciformis (Wulfen) J.V. Lamouroux. 2020. 49 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal do Ceará, Fortaleza, 2020.http://www.repositorio.ufc.br/handle/riufc/55506Venous thrombosis is the main cause of current morbidity and mortality. It is estimated that 2 / 1,000 individuals suffer from this disease. Antithrombotic drugs are commonly used as a prophylactic measure by those who are predisposed to thrombus formation. The most wellknown and used antithrombotics are Unfractionated Heparin (UFH) and Low Molecular Weight Heparin (LMWH), the second being obtained by depolymerizing the first. Because these drugs are produced in animals and have serious side effects such as hemorrhage, there is a demand for the discovery of new antithrombotic drugs of non-animal origin and with reduced side effects. It is known in the literature that sulfated polysaccharides from red marine algae have antithrombotic activity. This work aimed to evaluate the antithrombotic potential of the acid hydrolysis product of sulfated polysaccharides extracted from the red seaweed Hypnea musciformis (Wulfen) J.V. Lamouroux. A hydrolysis design was carried out to obtain sulfated galactans of different molecular weights. The molecular weight of the hydrolyzate was estimated by Gel Permeation Chromatography (GPC) and characterized by the presence of sulfation and functional groups characteristic by Infrared. Four samples of different molecular weights were selected to investigate their antithrombotic activity, the EX 1, 5 and 7 and the intact polysaccharide (PS-Hm). The in vitro antithrombotic activity was analyzed by the tests of partially activated thromboplastin time (APTT) and prothrombin time (TP), both using LMWH CLEXANE ® as a positive control. Only the intact PS-Hm and the EX 5 prolonged the clotting time in the APTT, and none of the analyzed samples influenced the TP. The bleeding time test was performed to assess the bleeding tendency with intact PS-Hm and EX 5, using LMWH CLEXANE ® as a positive control. The analyzed samples had no significant difference in relation to the negative control and both samples showed a hemorrhagic tendency much lower than the positive control. The results indicate that the antithrombotic and anticoagulant activity is related to the molecular weight of the sulfated polysaccharide, and that the reduction in molecular weight can reduce the hemorrhagic tendency. Such results suggest that the samples are candidates for new antithrombotic drugs, however more tests are needed to confirm the activity, such as the model of venous thrombosis in rats.Trombose venosa é a maior causa de morbimortalidade atual, Estima-se que 2/1.000 indivíduos sofram de tal doença. Medicamentos antitrombóticos são comumente utilizados como medida profilática por quem tem predisposição a formação de trombos. Os antitrombóticos mais conhecidos e utilizados são a Heparina Não Fracionada (HNF) e a Heparina de Baixo Peso Molecular (HBPM), sendo a segunda obtida pela despolimerização da primeira. Por estes medicamentos terem origem animal e apresentarem efeitos colaterais graves como hemorragia, há a demanda para a descoberta de novas drogas antitrombóticas de origem não-animal e com reduzidos efeitos colaterais. É conhecido na literatura que polissacarídeos sulfatados de algas marinhas vermelhas apresentam atividade antitrombótica. O presente trabalho teve como objetivo avaliar o potencial antitrombótico do produto da hidrólise ácida de polissacarídeos sulfatados extraídos da alga marinha vermelha Hypnea musciformis (Wulfen) J.V. Lamouroux. Foi realizado um delineamento de hidrólise afim de obter galactanas sulfatadas de diferentes pesos moleculares. O peso molecular do hidrolisado foi estimado por Cromatografia de Permeação em Gel (GPC) e caracterizado quanto a presença de sulfatação e grupos funcionais característicos por Infravermelho. Foram selecionadas 4 amostras de pesos moleculares distintos para investigar sua atividade antitrombótica, os EX 1, 5 e 7 e o polissacarídeo íntegro. A atividade antitrombótica in vitro foi analisada pelos testes de tempo de tromboplastina parcialmente ativado (TTPA) e tempo de protrombina (TP), ambos usando a HBPM CLEXANE ® como controle positivo. Apenas o PS-Hm íntegro e o EX 5 prolongaram o tempo de coagulação no TTPA, e nenhuma das amostras analisadas apresentou efeito no TP. Foi feito o teste de tempo de sangramento para avaliar a tendência hemorrágica com o PS-Hm íntegro e o EX 5, usando a HBPM CLEXANE ® como controle positivo. As amostras analisadas não tiveram diferença significativa em relação ao controle negativo e ambas as amostras apresentaram uma tendência hemorrágica muito inferior ao controle positivo. Os resultados apontam que a atividade antitrombótica e anticoagulante tem relação ao peso molecular do polissacarídeo sulfatado, e que a redução no peso molecular é capaz de reduzir a tendência hemorrágica. Tais resultados sugerem que as amostras são candidatas para a novas drogas antitrombóticas, contudo mais ensaios se fazem necessários para confirmar a atividade, como o modelo de trombose venosa em ratos.AnticoagulantesHidróliseMacroalgasMetodologia de superfície de respostaPolissacarídeos sulfatadosPotencial antitrombótico de hidrolisado ácido de polissacarídeos sulfatados de Hypnea musciformis (Wulfen) J.V. LamourouxAntitrombotic potential of the acid hydrolyzate of sulphated polysaccharides of Hypnea musciformis (Wulfen) J.V. Lamourouxinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/55506/4/license.txt8a4605be74aa9ea9d79846c1fba20a33MD54ORIGINAL2020_dis_clpeixoto.pdf2020_dis_clpeixoto.pdfapplication/pdf292564http://repositorio.ufc.br/bitstream/riufc/55506/3/2020_dis_clpeixoto.pdf88c1f71863336f0cec9fd335ab43511cMD53riufc/555062020-11-27 13:25:16.329oai:repositorio.ufc.br:riufc/55506Tk9URTogUExBQ0UgWU9VUiBPV04gTElDRU5TRSBIRVJFClRoaXMgc2FtcGxlIGxpY2Vuc2UgaXMgcHJvdmlkZWQgZm9yIGluZm9ybWF0aW9uYWwgcHVycG9zZXMgb25seS4KCk5PTi1FWENMVVNJVkUgRElTVFJJQlVUSU9OIExJQ0VOU0UKCkJ5IHNpZ25pbmcgYW5kIHN1Ym1pdHRpbmcgdGhpcyBsaWNlbnNlLCB5b3UgKHRoZSBhdXRob3Iocykgb3IgY29weXJpZ2h0Cm93bmVyKSBncmFudHMgdG8gRFNwYWNlIFVuaXZlcnNpdHkgKERTVSkgdGhlIG5vbi1leGNsdXNpdmUgcmlnaHQgdG8gcmVwcm9kdWNlLAp0cmFuc2xhdGUgKGFzIGRlZmluZWQgYmVsb3cpLCBhbmQvb3IgZGlzdHJpYnV0ZSB5b3VyIHN1Ym1pc3Npb24gKGluY2x1ZGluZwp0aGUgYWJzdHJhY3QpIHdvcmxkd2lkZSBpbiBwcmludCBhbmQgZWxlY3Ryb25pYyBmb3JtYXQgYW5kIGluIGFueSBtZWRpdW0sCmluY2x1ZGluZyBidXQgbm90IGxpbWl0ZWQgdG8gYXVkaW8gb3IgdmlkZW8uCgpZb3UgYWdyZWUgdGhhdCBEU1UgbWF5LCB3aXRob3V0IGNoYW5naW5nIHRoZSBjb250ZW50LCB0cmFuc2xhdGUgdGhlCnN1Ym1pc3Npb24gdG8gYW55IG1lZGl1bSBvciBmb3JtYXQgZm9yIHRoZSBwdXJwb3NlIG9mIHByZXNlcnZhdGlvbi4KCllvdSBhbHNvIGFncmVlIHRoYXQgRFNVIG1heSBrZWVwIG1vcmUgdGhhbiBvbmUgY29weSBvZiB0aGlzIHN1Ym1pc3Npb24gZm9yCnB1cnBvc2VzIG9mIHNlY3VyaXR5LCBiYWNrLXVwIGFuZCBwcmVzZXJ2YXRpb24uCgpZb3UgcmVwcmVzZW50IHRoYXQgdGhlIHN1Ym1pc3Npb24gaXMgeW91ciBvcmlnaW5hbCB3b3JrLCBhbmQgdGhhdCB5b3UgaGF2ZQp0aGUgcmlnaHQgdG8gZ3JhbnQgdGhlIHJpZ2h0cyBjb250YWluZWQgaW4gdGhpcyBsaWNlbnNlLiBZb3UgYWxzbyByZXByZXNlbnQKdGhhdCB5b3VyIHN1Ym1pc3Npb24gZG9lcyBub3QsIHRvIHRoZSBiZXN0IG9mIHlvdXIga25vd2xlZGdlLCBpbmZyaW5nZSB1cG9uCmFueW9uZSdzIGNvcHlyaWdodC4KCklmIHRoZSBzdWJtaXNzaW9uIGNvbnRhaW5zIG1hdGVyaWFsIGZvciB3aGljaCB5b3UgZG8gbm90IGhvbGQgY29weXJpZ2h0LAp5b3UgcmVwcmVzZW50IHRoYXQgeW91IGhhdmUgb2J0YWluZWQgdGhlIHVucmVzdHJpY3RlZCBwZXJtaXNzaW9uIG9mIHRoZQpjb3B5cmlnaHQgb3duZXIgdG8gZ3JhbnQgRFNVIHRoZSByaWdodHMgcmVxdWlyZWQgYnkgdGhpcyBsaWNlbnNlLCBhbmQgdGhhdApzdWNoIHRoaXJkLXBhcnR5IG93bmVkIG1hdGVyaWFsIGlzIGNsZWFybHkgaWRlbnRpZmllZCBhbmQgYWNrbm93bGVkZ2VkCndpdGhpbiB0aGUgdGV4dCBvciBjb250ZW50IG9mIHRoZSBzdWJtaXNzaW9uLgoKSUYgVEhFIFNVQk1JU1NJT04gSVMgQkFTRUQgVVBPTiBXT1JLIFRIQVQgSEFTIEJFRU4gU1BPTlNPUkVEIE9SIFNVUFBPUlRFRApCWSBBTiBBR0VOQ1kgT1IgT1JHQU5JWkFUSU9OIE9USEVSIFRIQU4gRFNVLCBZT1UgUkVQUkVTRU5UIFRIQVQgWU9VIEhBVkUKRlVMRklMTEVEIEFOWSBSSUdIVCBPRiBSRVZJRVcgT1IgT1RIRVIgT0JMSUdBVElPTlMgUkVRVUlSRUQgQlkgU1VDSApDT05UUkFDVCBPUiBBR1JFRU1FTlQuCgpEU1Ugd2lsbCBjbGVhcmx5IGlkZW50aWZ5IHlvdXIgbmFtZShzKSBhcyB0aGUgYXV0aG9yKHMpIG9yIG93bmVyKHMpIG9mIHRoZQpzdWJtaXNzaW9uLCBhbmQgd2lsbCBub3QgbWFrZSBhbnkgYWx0ZXJhdGlvbiwgb3RoZXIgdGhhbiBhcyBhbGxvd2VkIGJ5IHRoaXMKbGljZW5zZSwgdG8geW91ciBzdWJtaXNzaW9uLgo=Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2020-11-27T16:25:16Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Potencial antitrombótico de hidrolisado ácido de polissacarídeos sulfatados de Hypnea musciformis (Wulfen) J.V. Lamouroux
dc.title.en.pt_BR.fl_str_mv Antitrombotic potential of the acid hydrolyzate of sulphated polysaccharides of Hypnea musciformis (Wulfen) J.V. Lamouroux
title Potencial antitrombótico de hidrolisado ácido de polissacarídeos sulfatados de Hypnea musciformis (Wulfen) J.V. Lamouroux
spellingShingle Potencial antitrombótico de hidrolisado ácido de polissacarídeos sulfatados de Hypnea musciformis (Wulfen) J.V. Lamouroux
Peixoto, Caroline Landim
Anticoagulantes
Hidrólise
Macroalgas
Metodologia de superfície de resposta
Polissacarídeos sulfatados
title_short Potencial antitrombótico de hidrolisado ácido de polissacarídeos sulfatados de Hypnea musciformis (Wulfen) J.V. Lamouroux
title_full Potencial antitrombótico de hidrolisado ácido de polissacarídeos sulfatados de Hypnea musciformis (Wulfen) J.V. Lamouroux
title_fullStr Potencial antitrombótico de hidrolisado ácido de polissacarídeos sulfatados de Hypnea musciformis (Wulfen) J.V. Lamouroux
title_full_unstemmed Potencial antitrombótico de hidrolisado ácido de polissacarídeos sulfatados de Hypnea musciformis (Wulfen) J.V. Lamouroux
title_sort Potencial antitrombótico de hidrolisado ácido de polissacarídeos sulfatados de Hypnea musciformis (Wulfen) J.V. Lamouroux
author Peixoto, Caroline Landim
author_facet Peixoto, Caroline Landim
author_role author
dc.contributor.author.fl_str_mv Peixoto, Caroline Landim
dc.contributor.advisor1.fl_str_mv Moreira, Renato de Azevedo
contributor_str_mv Moreira, Renato de Azevedo
dc.subject.por.fl_str_mv Anticoagulantes
Hidrólise
Macroalgas
Metodologia de superfície de resposta
Polissacarídeos sulfatados
topic Anticoagulantes
Hidrólise
Macroalgas
Metodologia de superfície de resposta
Polissacarídeos sulfatados
description Venous thrombosis is the main cause of current morbidity and mortality. It is estimated that 2 / 1,000 individuals suffer from this disease. Antithrombotic drugs are commonly used as a prophylactic measure by those who are predisposed to thrombus formation. The most wellknown and used antithrombotics are Unfractionated Heparin (UFH) and Low Molecular Weight Heparin (LMWH), the second being obtained by depolymerizing the first. Because these drugs are produced in animals and have serious side effects such as hemorrhage, there is a demand for the discovery of new antithrombotic drugs of non-animal origin and with reduced side effects. It is known in the literature that sulfated polysaccharides from red marine algae have antithrombotic activity. This work aimed to evaluate the antithrombotic potential of the acid hydrolysis product of sulfated polysaccharides extracted from the red seaweed Hypnea musciformis (Wulfen) J.V. Lamouroux. A hydrolysis design was carried out to obtain sulfated galactans of different molecular weights. The molecular weight of the hydrolyzate was estimated by Gel Permeation Chromatography (GPC) and characterized by the presence of sulfation and functional groups characteristic by Infrared. Four samples of different molecular weights were selected to investigate their antithrombotic activity, the EX 1, 5 and 7 and the intact polysaccharide (PS-Hm). The in vitro antithrombotic activity was analyzed by the tests of partially activated thromboplastin time (APTT) and prothrombin time (TP), both using LMWH CLEXANE ® as a positive control. Only the intact PS-Hm and the EX 5 prolonged the clotting time in the APTT, and none of the analyzed samples influenced the TP. The bleeding time test was performed to assess the bleeding tendency with intact PS-Hm and EX 5, using LMWH CLEXANE ® as a positive control. The analyzed samples had no significant difference in relation to the negative control and both samples showed a hemorrhagic tendency much lower than the positive control. The results indicate that the antithrombotic and anticoagulant activity is related to the molecular weight of the sulfated polysaccharide, and that the reduction in molecular weight can reduce the hemorrhagic tendency. Such results suggest that the samples are candidates for new antithrombotic drugs, however more tests are needed to confirm the activity, such as the model of venous thrombosis in rats.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-11-27T16:22:33Z
dc.date.available.fl_str_mv 2020-11-27T16:22:33Z
dc.date.issued.fl_str_mv 2020
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 PEIXOTO, Caroline Landim. Potencial antitrombótico de hidrolisado ácido de polissacarídeos sulfatados de Hypnea musciformis (Wulfen) J.V. Lamouroux. 2020. 49 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal do Ceará, Fortaleza, 2020.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/55506
identifier_str_mv PEIXOTO, Caroline Landim. Potencial antitrombótico de hidrolisado ácido de polissacarídeos sulfatados de Hypnea musciformis (Wulfen) J.V. Lamouroux. 2020. 49 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal do Ceará, Fortaleza, 2020.
url http://www.repositorio.ufc.br/handle/riufc/55506
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.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Ceará (UFC)
instname:Universidade Federal do Ceará (UFC)
instacron:UFC
instname_str Universidade Federal do Ceará (UFC)
instacron_str UFC
institution UFC
reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
collection Repositório Institucional da Universidade Federal do Ceará (UFC)
bitstream.url.fl_str_mv http://repositorio.ufc.br/bitstream/riufc/55506/4/license.txt
http://repositorio.ufc.br/bitstream/riufc/55506/3/2020_dis_clpeixoto.pdf
bitstream.checksum.fl_str_mv 8a4605be74aa9ea9d79846c1fba20a33
88c1f71863336f0cec9fd335ab43511c
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
repository.name.fl_str_mv Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)
repository.mail.fl_str_mv bu@ufc.br || repositorio@ufc.br
_version_ 1847793116321415168