title: Systemic effects induced by the venom of the snake Bothrops caribbaeus in a murine model.
abstract: Snakebite envenoming by Bothrops caribbaeus, an endemic viperid from the Lesser Antillean island of Saint Lucia, is clinically characterized by local tissue damage and systemic thrombosis that can lead to cerebral, myocardial or pulmonary infarctions and venous thromboses. Systemic effects (lethality, pulmonary hemorrhage, thrombocytopenia and coagulopathy) induced by intravenous (i.v.) administration of B. caribbaeus venom were studied in mice. The role of snake venom metalloproteinases (SVMPs) in these systemic alterations was assessed by inhibition with the chelating agent calcium disodium ethylenediaminetetraacetic acid (CaNa(2)EDTA). A snake C-type lectin-like (snaclec) and a type P-III hemorrhagic SVMP were isolated and characterized from this venom, and the effect of venom and the isolated snaclec on human platelet aggregation was studied in vitro. Results indicate that SVMPs play an important role in the overall toxicity of B. caribbaeus venom, being responsible for systemic hemorrhage and lethality, but not thrombocytopenia, whereas the isolated snaclec is involved in the thrombocytopenic effect. Both venom and snaclec induce platelet aggregation/agglutination. Moreover, the snaclec binds directly to glycoprotein Ib (GPIb) and induces agglutination in washed fixed platelets. On the other hand, B. caribbaeus venom hydrolyzed fibrinogen in vitro and induced a partial drop of fibrinogen levels with an increase in fibrin/fibrinogen degradation products (FDP) levels in vivo. The negative result for D-dimer (DD) in plasma is consistent with the lack of microscopic evidence of pulmonary thrombosis and endothelial cell damage. Likewise, no increments in plasma sE-selectin levels were detected. The absence of thrombosis in this murine model suggests that this effect may be species-specific.
authors.affiliation: Facultad de Farmacia, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Cristina
authors.initials: C
authors.lastname: Herrera
authors.forename: Alexandra
authors.initials: A
authors.lastname: Rucavado
authors.forename: David A
authors.initials: DA
authors.lastname: Warrell
authors.forename: José María
authors.initials: JM
authors.lastname: Gutiérrez
mesh_terms: D000818:Animals; D017837:Bothrops / Q000502:physiology*; D003029:Coagulants / Q000737:chemistry / Q000633:toxicity*; D003435:Crotalid Venoms / Q000737:chemistry / Q000201:enzymology / Q000633:toxicity*; D004195:Disease Models, Animal; D004492:Edetic Acid / Q000737:chemistry; D005340:Fibrinogen / Q000187:drug effects; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D007275:Injections, Intravenous; D037181:Lectins, C-Type / Q000008:administration & dosage / Q000737:chemistry; D008136:Longevity / Q000187:drug effects; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology; D008297:Male; D045726:Metalloproteases / Q000737:chemistry / Q000633:toxicity; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects; D013045:Species Specificity; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000473:pathology; D013927:Thrombosis / Q000139:chemically induced* / Q000473:pathology
chemical_list: D003029:Coagulants; D003435:Crotalid Venoms; D037181:Lectins, C-Type; D005340:Fibrinogen; D004492:Edetic Acid; D045726:Metalloproteases