title: The effect of fibrinolytic enzyme FIIa from Agkistrodon acutus venom on disseminated intravascular coagulation in rabbits.
abstract: A novel fibrinolytic enzyme, FII(a), was isolated from Agkistrodon acutus venom, which can degrade fibrin/fibrinogen and dissolve thrombus without activating plasminogen or influencing the activities of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1). In this study, we evaluated the effect of FII(a) on lipopolysaccharide (LPS)-induced experimental disseminated intravascular coagulation (DIC) in rabbits, through the continuous infusion of 100-microg/kg/h LPS for a period of 6 h. Seven groups were established: LPS control, FII(a) (0.1, 0.3, and 0.6 mg/kg/h, respectively), heparin control (100 IU/kg/h), heparin + FII(a) (heparin 100 IU/kg/h associated with FII(a) 0.3 mg/kg/h), and a saline control group. A continuous injection of LPS induced a gradual impairment in hemostatic parameters, kidney fibrin deposition, and a high mortality rate. The intravenous administration of FII(a) improved the concentration of fibrinogen, the activities of protein C, plasminogen, t-PA, antithrombin III (ATIII), and PAI-1. Kidney fibrin deposition and the mortality also decreased. In the in vitro experiments, FII(a) can degrade fibrin/fibrinogen and high-dose FII(a) enhanced the activity of protein C. These findings suggest that the effects of FII(a) on LPS-induced DIC were from fibrinogen degradation and enhanced protein C activity. The simultaneous administration of FII(a) and heparin further improved all the hemostatic parameters, including decreased kidney fibrin deposition, and none of the rabbits died within 24 h, which indicates that the effects were mediated by degradation of fibrin/fibrinogen together with thrombin inhibition. We conclude that FII(a) may be useful in the treatment of DIC.
authors.affiliation: Department of Pharmacology, Zhongshan Medical College, SUN Yat-Sen University, Guangzhou, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.forename: Xiu-Xia
authors.initials: XX
authors.lastname: Liang
authors.forename: Jia-Shu
authors.initials: JS
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Peng-Xin
authors.initials: PX
authors.lastname: Qiu
authors.forename: Guang-Mei
authors.initials: GM
authors.lastname: Yan
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000032:analysis; D003435:Crotalid Venoms / Q000201:enzymology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D005337:Fibrin / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006493:Heparin / Q000494:pharmacology; D007275:Injections, Intravenous; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008136:Longevity / Q000187:drug effects; D008297:Male; D008666:Metalloendopeptidases; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011486:Protein C / Q000032:analysis; D011817:Rabbits; D013927:Thrombosis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: C031442:Agkistrodon venoms; D003435:Crotalid Venoms; D005343:Fibrinolytic Agents; D008070:Lipopolysaccharides; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D000990:Antithrombin III; D005337:Fibrin; D006493:Heparin; D010959:Tissue Plasminogen Activator; C478420:FIIa; D008666:Metalloendopeptidases