Venous antithrombotic and anticoagulant activities of a fucoïdan fraction.
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 micrograms/ml, thrombin inhibition mediated by AT showed an apparent second-order rate constant (kapp) of 2 x 10(8) M-1 min-1, compared to 1.5 x 10(6) M-1 min-1 for the uncatalyzed reaction. The kapp value of thrombin inhibition via HCII was 1.17 x 10(9) M-1 min-1 at a fucoïdan concentration of 50 micrograms/ml, compared to 1.72 x 10(5) 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 micrograms/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.
Mauray
S
S
Laboratoire d'hématologie, Hôpital Necker-Enfants Malades, Paris, France.
Sternberg
C
C
Theveniaux
J
J
Millet
J
J
Sinquin
C
C
Tapon-Bretaudière
J
J
Fischer
A M
AM
D000818:Animals; D000925:Anticoagulants / Q000302:isolation & purification / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D005643:Fucose / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D011817:Rabbits; D012624:Seaweed / Q000201:enzymology
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D005643:Fucose