Platelet aggregation inhibitors from Bothrops alternatus snake venom.

Snake venoms are a complex mixture of proteins and peptides that can activate/inhibit platelet aggregation. Bothrops alternatus venom include three main families: metalloproteinases (SVMPs), serinoproteinases (SVSPs) and phospholipases A2 (PLA2s), among other minor components. In this work, we used inhibitor cocktails (containing Na2-EDTA, PMSF and/or pBPB) to investigate the effect of these three families and of baltergin (a PIII SVMP) on platelet aggregation by a turbidmetric method using a microplate reader. Cocktails 1 (active SVMPs) and 2 (active PLA2s) significantly reduced aggregation induced by ristocetin and collagen and by collagen and thrombin, respectively. Cocktail 3 (active SVSPs) showed a mild activation of aggregation, indicating the content of thrombin-like enzymes (TLEs) in this venom is low. Cocktail 4 (active minor components) displayed inhibitory effect with all agonists assayed (ristocetin, ADP, collagen and thrombin) but at higher IC50 values. Baltergin exhibited inhibitory effect when the catalytic domain was active for ristocetin-stimulated platelet aggregation and showed a non-enzymatic mechanism of inhibition when collagen was used as agonist. It was not able to disaggregate platelet thrombus. We conclude that B. alternatus venom is a source of natural inhibitors of platelet aggregation due to the action of SVMPs and PLA2s. Other minor components such as C-type lectins likely contribute to the antiplatelet effect. The interest in knowing the action of venom components on platelet function lies both in the understanding of the pathophysiology of snake bite envenomation and in their biotechnological application.

Venoms and Isolated Toxins from Snakes of Medical Impact in the Northeast Argentina: State of the Art. Potential Pharmacological Applications.

Among the ophidians that inhabit the Northeast of Argentina, the genus Bothrops such as B. alternatus and B. diporus species (also known as yararás) and Crotalus durisus terrificus (named cascabel), represent the most studied snake venom for more than thirty years. These two genera of venomous snakes account for the majority of poisonous snake envenomations and therefore, constitute a medical emergency in this region. This review presents a broad description of the compiled knowledge about venomous snakebite: its pathophysiological action, protein composition, isolated toxins, toxin synergism, toxin-antitoxin cross-reaction assays. Properties of some isolated toxins support a potential pharmacological application.