Um dermatam sulfato antitromb?tico do camar?o Litopenaeus vanammei inibe a inflama??o e angiog?nese

• Main Author: Palhares, Lais Cristina Gusm?o Ferreira
• Other Authors: 33615217420
• Language: Portuguese
• Published: Universidade Federal do Rio Grande do Norte 2016
• Subjects: CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA; Anti-inflamat?rio; Neovasculariza??o; Trombose; Trombina; Coagula??o; Glicosaminoglicano
• Online Access: http://repositorio.ufrn.br/handle/123456789/21229

Submitted by Automa??o e Estat?stica ([e-mail]) on 2016-08-16T22:23:12Z No. of bitstreams: 1 LaisCristinaGusmaoFerreiraPalhares_DISSERT.pdf: 1523874 bytes, checksum: 887759d06e609dbc7d0f9dd62eb7681f (MD5) === Approved for entry into archive by Arlan Eloi Leite Silva ([e-mail]) on 2016-08-23T21:38:40Z (GMT) No. of bitstreams: 1 LaisCristinaGusmaoFerreiraPalhares_DISSERT.pdf: 1523874 bytes, checksum: 887759d06e609dbc7d0f9dd62eb7681f (MD5) === Made available in DSpace on 2016-08-23T21:38:40Z (GMT). No. of bitstreams: 1 LaisCristinaGusmaoFerreiraPalhares_DISSERT.pdf: 1523874 bytes, checksum: 887759d06e609dbc7d0f9dd62eb7681f (MD5) Previous issue date: 2016-03-29 === A inflama??o ? composta de uma rea??o vascular e outra celular, conferindo diferentes rea??es de tecidos e c?lulas, tanto do ambiente intravascular, como o do ambiente extravascular. ? medida que o processo inflamat?rio ocorre, proteases da coagula??o, em especial a trombina (FIIa), s?o capazes de desencadear diversas respostas celulares na biologia vascular e por isso, frequentemente ? observada a ativa??o de outros sistemas biol?gicos, levando ? complica??es durante um evento inflamat?rio, como a trombose e a angiog?nese. Assim, mol?culas antagonistas desses eventos s?o modelos interessantes para o desenvolvimento de novos f?rmacos anti-inflamat?rios. Neste contexto, destacam-se os glicosaminoglicanos (GAGs), os quais interagem com diversas prote?nas envolvidas em processos biol?gicos importantes, incluindo inflama??o e coagula??o. Por essa raz?o, o presente trabalho teve por objetivo avaliar os potenciais anti-inflamat?rios, antitromb?tico, antiangiog?nico, bem como anticoagulante de GAGs do tipo dermatam sulfato (DS) extra?dos do cefalot?rax do camar?o Litopenaeus vannamei. O composto foi obtido ap?s prote?lise e purifica??o por cromatografia de troca-i?nica. Ap?s total digest?o por liases que digerem compostos tipo DS (condroitinase ABC), sua natureza do tipo DS foi revelada, sendo ent?o denominado DSL. O composto do camar?o mostrou reduzido efeito anticoagulante pelo ensaio de TTPa, por?m apresentou alta atividade anti-IIa, diretamente e via Cofator II da heparina. Sobre a inflama??o, o composto apresentou significativo efeito inibit?rio com redu??o de citocinas pr?-inflamat?rias. Potenciais inibit?rios foram relatados no ensaio antitromb?tico e antiangiog?nico, sendo este ?ltimo dose-dependente. Quanto ? atividade anti-hemost?tica, o polissacar?deo n?o induziu efeito hemorr?gico significativo. Assim, os resultados exibidos pelo composto tipo DS isolado do camar?o, apontam este glicosaminoglicano como alvo biotecnol?gico com perspectivas para o desenvolvimento de novas drogas multipotentes. === Inflammation is combined of a vascular and a cellular reaction, resulting in different cells and tissue responses, both the intravascular and extravascular environment. As the inflammatory process occurs, coagulation proteases, in particular thrombin (FIIa), are able to initiate various cellular responses in vascular biology and therefore is often observed activation of other biological systems, leading to complications during an event inflammatory, such as thrombosis and angiogenesis. Thus, antagonists molecules of these events are interesting models for the development of novel anti-inflammatory drugs. Thereby, it is worth stressing the glycosaminoglycans (GAGs), which are able to interact with several proteins involved in important biological processes, including inflammation and coagulation. Therefore, this study aimed to evaluate the anti-inflammatory, antithrombotic and anti-angiogenic potentials, as well anticoagulant of a dermatan sulfate-like GAG (DS) extracted from the Litopenaeus vannamei cephalotorax. The compound was obtained after proteolysis and purification by ion-exchange chromatography. After total digestion by DS-like compounds digesting lyases (chondroitinase ABC), the DS-like nature was revealed, and then called DSL. The shrimp compound showed reduced anticoagulant effect by the aPTT assay, but high anti-IIa activity, directly and through heparin cofactor II. On inflammation, the compound had a significant inhibitory effect with the reduction of proinflammatory cytokines. Potential Inhibitory were reported in the antithrombotic and anti-angiogenic assay, the latter being dose dependent. As for anti-hemostatic activity, the polysaccharides did not induced significant bleeding effect. Thus, the results shown by the shrimp DS-like compound indicate this glycosaminoglycan as a biotechnology target with prospects for the development of new multipotent drugs.