Antithrombotic and anticoagulant activity of depolymerized fragment of the glycosaminoglycan extracted from Stichopus japonicus Selenka.
The antithrombotic and anticoagulant activities of depolymerized fragment (DHG-1) of glycosaminoglycan extracted from Stichopus japonicus Selenka (FGAG) were compared with those of unfractionated heparin (UFH) or low molecular weight heparin (LMWH). DHG-1 at more than 0.3 mg/kg i.v. significantly prevented death of mice treated with thrombin (800 U/kg i.v.). Under the same conditions, FGAG, UFH and LMWH significantly prevented death of mice at more than 0.3, 0.3 and 0.6 mg/kg i.v., respectively. In normal plasma, the concentration required to double the activated partial thromboplastin time (doubling APTT) of DHG-1, FGAG, LMWH and UFH were 12.0, 2.4, 5.8, and 1.2 micrograms/ml, respectively. In antithrombin III (AT III)-depleted plasma, doubling APTT of DHG-1, FGAG, and UFH were 11.3, 2.1, and 18.5 micrograms/ml, respectively. Prothrombin activation in contact-activated plasma was inhibited completely for 60 s at doubling APTT by all glycosaminoglycans used in this study. DHG-1, however, showed much less antithrombin activity than UFH as tested by thrombin clotting time in plasma and chromogenic assay in the presence of AT III. Moreover, DHG-1 showed much less inhibitory activity on factor Xa, factor IXa, and glass surface-induced factor IXa generation than UFH. These results suggested that DHG-1 is one of the promising antithrombotic agents with quite different anticoagulant property from UFH or LMWH.
Suzuki
N
N
Taiho Pharmaceutical Co., Ltd, Tokushima, Japan.
Kitazato
K
K
Takamatsu
J
J
Saito
H
H
D000818:Animals; D000925:Anticoagulants / Q000302:isolation & purification; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests / Q000379:methods; D005343:Fibrinolytic Agents / Q000302:isolation & purification; D006025:Glycosaminoglycans / Q000302:isolation & purification / Q000494:pharmacology*; D006493:Heparin; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012616:Sea Cucumbers; D013927:Thrombosis / Q000517:prevention & control
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006025:Glycosaminoglycans; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin