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InibiÃÃo dos efeitos locais do veneno de Bothrops pauloensis por alcalÃides esteroidais de Solanum campaniforme Roem. & Schult. (Solanaceae). / Inhibition of the local effects of Bothrops pauloensis by steroidal alkaloids from Solanum campaniforme Roem. & Schult. (Solanaceae).Roberta Jeane Bezerra Jorge 07 July 2011 (has links)
Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Envenenamentos por serpentes sÃo um importante problema de saÃde muito difundido em paÃses tropicais. Entre as espÃcies mais perigosas da AmÃrica do Sul encontra-se o gÃnero Bothrops. Acidentes ofÃdicos causados por espÃcies Bothrops podem desenvolver rapidamente dano tecidual local grave, incluindo edema, hemorragia, mionecrose, ulceraÃÃo de pele e dor. A soroterapia tradicional tem eficÃcia limitada contra esses efeitos. Compostos naturais isolados de plantas, principalmente a partir de espÃcies usadas na medicina popular para tratar envenenamentos de serpente, podem ser uma boa alternativa para encontrar novos compostos para melhorar o tratamento do envenenamento e minimizar as sequelas das vÃtimas. Atividade antiofÃdica dos novos alcalÃides esteroidais: 1 -22,23-epoxi-solanida-1,4,9-trien-3-ona (1), 2-22,23-epoxi-solanida-1,4-dien-3-ona (2) 3-3,9-dihidroxi-22,23-epoxi-9-10-secosolanida-1,3,5(10)-trieno (3) isolados das folhas de Solanum campaniforme foram testados atravÃs da inibiÃÃo da atividade fosfolipÃsica, atividade proteolÃtica, miotoxicidade, hemorragia e necrose induzidas pelo veneno de Bothrops pauloensis. Os trÃs compostos foram capazes de inibir completamente a liberaÃÃo de creatina quinase de mÃsculos estriados esquelÃticos e minimizar as alteraÃÃes histolÃgicas sem inibir a atividade fosfolipÃsica A2 do veneno total de B. pauloensis. A inibiÃÃo da miotoxicidade parece ser independente da atividade catalÃtica de fosfolipase (PLA2) e pode estar relacionada à inibiÃÃo da PLA2 Lys 49, enzimaticamente inativas, e / ou uma aÃÃo indireta sobre metaloproteinases. Houve tambÃm, a inibiÃÃo da atividade proteolitica do veneno em diferentes substratos com os trÃs alcaloides A hemorragia, bem como a necrose de pele, ambas induzidas por metaloproteases presentes no veneno, foram reduzidas na presenÃa dos alcalÃides 1 e 2, mas nÃo com o alcalÃide 3. A inibiÃÃo das atividades proteolÃticas e a reduÃÃo dos efeitos hemorrÃgicos e necrosantes induzidas pelo vBp, principalmente atribuÃdos aos alcalÃides 1 e 2, podem estar associadas com a interaÃÃo destes compostos com as metaloproteases presentes no veneno e/ou com Ãons metÃlicos bivalentes necessÃrios para sua aÃÃo. / Snake envenoming is an important health problem widespread in tropical countries. Among the most dangerous species in South America is the Bothrops genus. Snakebites accidents caused by Bothrops species quickly develop severe local tissue damage, including swelling, hemorrhage, myonecrosis, skin ulceration and pain. The traditional serum therapy has limited effectiveness against these effects. Natural compounds isolated from plants, mainly from species used in folk medicine to treat snakebite, are a good choice to find new lead compounds to improve the snakebite treatment and minimize the sequelae of the victims. Antiophidic activity of the new steroidal alkaloids: 22-epoxy-solanide-1,4,9-trien-3-one (1), 22-epoxy-solanide-1,4-dien-3-one (2) and 3,9-dihydroxy-22,23-epoxy-9,10-secosolanida-1,3,5(10)-triene (3) isolated from leaves of Solanum campaniforme was tested through inhibition of phospholipasic activity, proteolytic activity, myotoxicity, hemorrhage and necrosis induced by Bothrops pauloensis venom. The three compounds were able to complete inhibit the creatine kinase release from skeletal muscles and minimize the histological changes, without inhibiting the phospholipasic A2 activity of whole venom. The inhibition of myotoxicity appears to be independent of catalytic activity of phospholipase A2 (PLA2) and may be related to inhibition of PLA2 Lys 49, enzymatically inactive, and / or an indirect action on metalloproteinases. There was also, the inhibition of proteolytic activity of the venom on different substrates with three alkaloids. Hemorrhage as well as skin necrosis, both induced by metalloproteases present in the venom, were reduced in the presence of alkaloids 1 and 2 , but not with the alkaloid 3. Inhibition of proteolytic activities and the reduction of hemorrhagic and necrotizing effects induced by vBp, mainly attributed to the alkaloids 1 and 2, may be associated with the interaction of these compounds with the metalloproteases present in the venom and / or divalent metal ions required for their action.
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