Effects of crotoxin, a neurotoxin from Crotalus durissus terrificus snake venom, on human endothelial cells.

Vascular endothelium plays an important modulatory role due to the production of molecules that mediate vasomotricity, inflammation, and leukocyte adhesion and rolling. Here we addressed whether crotoxin (25-200 µg/mL) - the main component of Crotalus durissus terrificus snake venom - interferes with cell viability, apotosis/necrosis, and cell response to oxidative stress in human umbilical vein endothelial cells (HUVEC) in vitro. We also examined whether crotoxin alters the levels of interleukins, adhesion molecules, and endothelial vasoactive factors in HUVEC cells treated or not with lipopolysaccharide (LPS; 1 µg/mL; 24 h). Crotoxin was not cytotoxic towards HUVEC cells, and downregulated the LPS-induced production of adhesion molecules (VCAM-1, ICAM-1, and E-selectin), vasoactive factors (endothelin-1 and prostaglandin I2), and interleukins (IL-6, IL-8, and IL1ß), as well as protected cells against H2O2-induced oxidative stress. Hence, crotoxin played anti-inflammatory, antioxidant, immunomodulating, and vasoactive actions on HUVEC cells, in vitro. Considering that the initial stages of atherosclerosis is characterized by vasoconstriction, increased levels of adhesion molecules, inflammatory cytokines, and oxidative stress in the vascular endothelium; and crotoxin downmodulated all these events, our findings indicate that the actions of crotoxin here demonstrated suggest that it may have an anti-atherogenic action in vivo, which deserves to be tested in future studies.

Crotoxin, a neurotoxin from Crotalus durissus terrificus snake venom, as a potential tool against thrombosis development.

Endothelium plays an important modulatory role due to the synthesis and secretion of molecules that act on hemostasis and fibrinolysis. As there are no literature data about the effect of crotoxin (CTX) - the main component of Crotalus durissus terrificus snake venom - on human endothelial cells, the present study examined how CTX (25-200 µg/mL) affects the endothelial production of the hemostatic factors antithrombin III, protein C, protein S, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), and vWF in human umbilical vein endothelial cells (HUVEC) in vitro. Production of hemostatic factors was assessed in HUVEC cells treated with CTX (25-200 µg/mL) in the presence or absence of lypopolysaccharide (LPS; 1 µg/mL; 24 h). We found that CTX alone did not exert pro- or anticoagulant effect on hemostasis, and pro- or antifibrinolytic effect on fibrinolysis. LPS alone had procoagulant (increased vWF and reduced protein C and S levels) and antifibrinolytic action (reduced t-PA and increased PAI-1 levels). However, CTX exerted anticoagulant and profibrinolytic action in the presence of LPS by lowering the levels of vWF and t-PA and elevating the levels of protein C and PAI-1. Therefore can be used as a potential tool against thrombosis development.