Convulsiva

Silveira, LB(1); Marcussi, S(2); Ticli, FK(3); Urzeda, MA(2); Biondo, R(2); França, SC(2); Pereira, PS(2); Soares, AM(2)

Natural And Artificial Inhibitors Of Snake Venom Phospholipases A₂

Phospholipases A₂ (PLA₂) from snake venoms induce different toxic and pharmacological effects including myotoxicity, edema, hypotension, platelet aggregation inhibition, convulsion, anticoagulation and others. Natural PLA₂ inhibitors were found in different organisms as plants, marine animals, snake and opossum plasmas. Functional characterization of natural (MMV from Taberna montana extract; manoalid A, from marine animal; heparin, from human blood; BmjMIP, from B. moojeni plasma; CAB from opossum plasma) and synthetic inhibitors (manoalid B, p-bromophenacil bromide BPB, EDTA), upon the enzymatic and pharmacological activity of PLA2 from Bothrops and Crotalus snake venome. PLA₂ was assayed in gels, while the myotoxic and edema inducing were evaluated in vivo. PrTX-I and III (from B. pirajai), BthTX-I and II (from B. jararacussu), crotoxin and CB (from C. durissus terrificus), in the presence or absence of different inhibitors, following an incubation of 30 minutes at 37ºC were used. Among the natural inhibitors, the following decreasing range of activity was observed: BmjMIP > manoalid A > CAB > heparin > MMV; for the synthetic ones, the sequence was: BPB > manoalid B > EDTA. Different levels of inhibition among PLA_2s from Bothrops and Crotalus venoms were also detected. Natural inhibitors were more efficient than synthetic ones for neutralization of the toxic and enzymatic effects induced by PLA_2s. Structural and interaction studies are needed to a better understanding of inhibitory effect in order to design new models of more potent synthetic inhibitors.