ABSTRACT
Jararhagin, a haemorrhagic metalloproteinase from Bothrops jararaca venom, plays an important role in systemic as well as local haemorrhage. In this study, the effect of jararhagin on the fibrinolytic system was investigated. The fibrinolytic activity of various kinds of animal plasmas was measured by the fibrin plate method. No activity was detected in plasma alone. However, after mixing plasma with jararhagin, strong fibrinolytic activity was recorded in guinea-pig, horse, dog, rabbit and human plasmas. The mechanism of the increase of firbinolytic activity by jararhagin was studied further in guinea-pig plasma. Fibrin-zymographic studies indicated that jararhagin increased tissue-type plasminogen activator (tPA) activity by the dissociation of a complex of tPA with type 1 plasminogen activator inhibitor (PAI-1). alpha 2-Plasmin inhibitor (alpha 2-PI) activity in the plasma was measured using a synthetic chromogenic substrate method after incubation with jararhagin. The alpha 2-PI activity in the plasma decreased in both time-dependent and dose-dependent manners. These in vitro results suggest that, in some animal plasmas, jararhagin increases plasma fibrinolytic activity by causing dissociation of the tPA/PAI-1 complex and by the inactivation of alpha 2-PI. It is possible that this direct action of jararhagin on the enhancement of plasma fibrinolytic activity may contribute to the aetiology of systemic haemorrhage frequently observed in human victims of B. jararaca envenoming.
Subject(s)
Crotalid Venoms/toxicity , Fibrinolysis/drug effects , Hemorrhage/chemically induced , Metalloendopeptidases/toxicity , Platelet Aggregation Inhibitors/toxicity , Serine Proteinase Inhibitors/toxicity , Animals , Blood Proteins/metabolism , Crotalid Venoms/administration & dosage , Crotalid Venoms/isolation & purification , Crotalid Venoms/metabolism , Dogs , Electrophoresis, Polyacrylamide Gel , Guinea Pigs , Horses , Humans , Metalloendopeptidases/administration & dosage , Metalloendopeptidases/isolation & purification , Metalloendopeptidases/metabolism , Plasminogen Activator Inhibitor 1/metabolism , Plasminogen Activator Inhibitor 1/toxicity , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/metabolism , Rabbits , Serine Proteinase Inhibitors/metabolism , Tissue Plasminogen Activator/drug effects , Tissue Plasminogen Activator/metabolism , alpha-2-Antiplasmin/analysis , alpha-2-Antiplasmin/metabolism , Bothrops jararaca VenomABSTRACT
The bites of six species of venomous elapid snakes in Central Province Papua New Guinea produce similar clinical syndromes. Optimal management of envenomed patients involves the use of monospecific antivenom. In this study, Venom Detection Kits (VDKs) (CSL Diagnostics, Melbourne) were used to try to make a specific diagnosis in envenomed patients at their admission. VDKs detected venom in admission bite site swabs from 39 to 46 patients (85%). Thirty-eight of these patients were shown to have been bitten by taipans. In all cases where venom was detected by the VDK, this correlated with subsequent laboratory enzyme immunoassay results. Selective use of VDKs in Central Province could allow more widespread use of monospecific antivenoms and produce considerable financial savings.
