Venous Antithrombotic and Anticoagulant Activities of a Fucoïdan Fraction

DOI PDF 被引用文献2件

書誌事項

公開日
1995
DOI
  • 10.1055/s-0038-1649927
公開者
Georg Thieme Verlag KG

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<jats:title>Summary</jats:title><jats:p>Fucoïdans catalyse thrombin inhibition by antithrombin (AT) and heparin cofactor II (HCII); their affinity for each serpin varies according to the seaweed species from which they are extracted, as well as their chemical composition and molecular weight. We extracted a homogeneous fucoïdan fraction from Ascophyllum nodosum, a brown seaweed, and tested its anticoagulant and antithrombotic activities. At a fucoïdan concentration of 3.75 µg/ml, thrombin inhibition mediated by AT showed an apparent second-order rate constant (kapp) of 2 × 108 M-1 min-1, compared to 1.5 × 106 M-1 min-1 for the uncatalyzed reaction. The kapp value of thrombin inhibition via HCII was 1.17 × 109 M-1 min-1 at a fucoïdan concentration of 50 µg/ml, compared to 1.72 × 105 M-1 min-1 for the uncatalyzed reaction. In a Wessler model of venous thrombosis, the fucoïdan fraction, injected intravenously to rabbits 10 min before thrombosis induction, exhibited antithrombotic activity: 1.8 mg/kg was the dose which inhibited F Xa-induced thrombus formation by 80% (ED80), compared to a heparin ED80 of 0.1 mg/kg. At this ED80 the antithrombotic effect of the fucoïdan persisted longer than that of heparin (30 min versus 15 min). The thrombin clotting time (TCT) was significantly prolonged (73 s versus control 29 s, compared to 53 s with heparin) 10 min after a fucoïdan bolus infusion giving a plasma fucoïdan concentration of 14.6 ± 2.7 µg/ml. The bleeding time was slightly increased after fucoïdan infusion at the ED80. Fucoïdan extracted from marine flora thus shows promise as an antithrombotic drug.</jats:p>

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