Inibição dos efeitos locais do veneno de Bothrops pauloensis por alcalóides esteroidais de Solanum campaniforme Roem. & Schult. (Solanaceae)

Abstract

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.