Anticoagulant activity of sulfatide and its anti-thrombotic effect in rabbit.
The mechanism of anticoagulant activity of sulfatide (galactosylceramide I3-sulfate), which exists in serum lipoproteins of various mammals except rodents, was investigated, together with the pharmacological effects of the glycolipid on the blood coagulation system in rabbits. The sulfatide was shown to be an effective anticoagulant when it was added in vitro in the form of pure micelle without auxiliary lipids such as phosphatidylcholine and/or cholesterol. The anticoagulant activity of synthetic galactosylceramide I6-sulfate, a positional isomer with respect to the sulfate group, was stronger than that of the sulfatide. The anticoagulant activity was specifically inhibited by anti-sulfatide antibody. The study on the pharmacological effects of sulfatide showed that the fibrin-precipitation time after single injection of the lipid (10 mg/kg body weight) into rabbits increased 2.5-fold compared with the normal level, and the maximum effect was observed 1 h after the injection. The half-life of anticoagulant activity was 5 h. These results suggest that sulfatide may be effective for the prevention of thrombosis. Sulfatide may be safer than other anticoagulant drugs, because it is a natural component of serum lipoproteins. Further, it may well play an essential role as an endogenous anticoagulant in mammals. Unlike heparin, sulfatide failed to inhibit thrombin and coagulation factor Xa activities in the presence of antithrombin III, indicating that the anticoagulant mechanism of sulfatide is independent of antithrombin III. These results indicate that the anticoagulant activity of sulfatide is potent and specific, and the lipid may be available as a useful and safe antithrombotic drug.
Hara
A
A
Department of Lipid Biochemistry, Shinshu University School of Medicine, Nagano.
Kutsukake
Y
Y
Uemura
K I
KI
Taketomi
T
T
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D065427:Factor Xa Inhibitors; D066298:In Vitro Techniques; D010713:Phosphatidylcholines / Q000494:pharmacology; D011817:Rabbits; D013433:Sulfoglycosphingolipids / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors; D013927:Thrombosis / Q000517:prevention & control*
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D010713:Phosphatidylcholines; D013433:Sulfoglycosphingolipids; D000990:Antithrombin III; D002784:Cholesterol; C010942:1,2-distearoyllecithin; D013917:Thrombin