title: Thrombolytic and Antiplatelet Effects of a Novel Plasminogen Activator from the Venom of Gloydius Brevicaudus Viper.
abstract: OBJECTIVE
  To investigate the thrombolytic and antiplatelet effects of a novel plasminogen activator from the venom of the Gloydius brevicaudus viper (GBV-PA) in vitro and in vivo.
  
  
  METHODS
  Thrombolytic experiments were performed in rabbit models of ear vein thrombosis and carotid artery thrombosis and in dog model of acute cerebral infarction. Inhibition of thrombus formation was evaluated in rat inferior vena cava thrombosis model and ferric chloride-induced arterial thrombosis. In vitro, we assayed the antithrombotic effect of GBV-PA on rabbit blood clots, euglobulin lysis time (ELT) of rabbit plasma, and ADP-induced platelet aggregation.
  
  
  RESULTS
  GBV-PA intravenous administration significantly reduced vascular recanalization times of rabbit ear veins thrombosis and thrombus weight of rabbit carotid artery thrombosis. The arterial recanalization rates were dose- and time-dependently improved after the administration of GBV-PA in canine acute cerebral infarction model. Thrombus length and weight were significantly reduced by GBV-PA both in rat inferior vena cava and ferric chloride-induced arterial thrombosis models. Thrombus formation in the blood of rabbits that were administered of GBV-PA was also inhibited. GBV-PA radically reduced plasma ELT of the rabbit's blood clots. ADP-induced platelet aggregation was inhibited by GBV-PA in a dose-dependent manner with a half-maximal inhibitory concentration of 19.9 μg/mL.
  
  
  CONCLUSIONS
  This study demonstrates that GBV-PA is a thrombolytic and antiplatelet agent. It has significant antithrombotic effects on various in vitro and in vivo experimental models of thrombosis. The mechanisms that underline its antithrombotic effects were related to GBV-PA's capabilities of increasing fibrinolytic activity and inhibition of platelet aggregation.
authors.affiliation: School of Pharmacy, Fujian Medical University.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Lili
authors.initials: L
authors.lastname: Lin
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ningning
authors.initials: N
authors.lastname: Zhao
authors.forename: Linqun
authors.initials: L
authors.lastname: Wu
authors.forename: Jianji
authors.initials: J
authors.lastname: Chen
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wu
authors.forename: Guotu
authors.initials: G
authors.lastname: Wu
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Lin
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Yunlu
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D051379:Mice; D010960:Plasminogen Activators / Q000737:chemistry / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D015912:Thrombolytic Therapy / Q000379:methods*; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome; D014757:Viper Venoms / Q000737:chemistry*
chemical_list: D010975:Platelet Aggregation Inhibitors; D014757:Viper Venoms; D010960:Plasminogen Activators