Effect of Low Molecular Weight Fucoidan and Low Molecular Weight Heparin in a Rabbit Model of Arterial Thrombosis

Abstract

Background: Therapeutic use of unfractionated heparin and low molecular weight heparins (LMWHs) is limited by hemorrhagic adverse effects. We compared the antithrombotic effect of LMW fucoidan (LMWF) and LMWH in an experimental model. Methods: Thrombosis was induced in femoral arteries of male New Zealand White rabbits by in situ induction of endothelial apoptosis with staurosporine (10^–5M for 30 min). Starting the day before apoptosis induction, the animals received subcutaneous LMWF (15 mg/kg), LMWH (enoxaparin 2.5 mg/kg) or saline solution (control group) twice a day for 4 days. Results: The degrees of apoptosis and endothelial denudation were similar in the 3 groups. The thrombotic score was significantly lower in the LMWF group than in the LMWH and control groups (p = 0.01). Tissue factor expression was significantly lower in the LMWF group than in the control and LMWH groups (p = 0.01). The plasma concentration of tissue factor pathway inhibitor was significantly increased after LMWF injection (137 ± 28 vs. 102 ± 17; p = 0.01), whereas no change was observed after LMWH treatment. LMWF did not prolong the bleeding time or decrease platelet aggregation. Conclusions: LMWF appeared to be more effective than LMWH for preventing arterial thrombosis in this experimental model. LMWF also had a lower hemorrhagic risk than LMWH.

Fucoidan Is a Novel Platelet Agonist for the C-type Lectin-like Receptor 2 (CLEC-2)

“…1 and 6). Previously, fucoidan has been show to have antithrombotic effects (41)(42)(43). The reason for such opposite effects of fucoidan on platelets may be due to different molecular weights of fucoidan.…”

Prospects for the therapeutic application of sulfated polysaccharides of brown algae in diseases of the cardiovascular system: review

“…High molecular weight fucans demonstrated a greater anticoagulant effect than structurally similar polysaccharides having lower molecular weight (Nishino & Nagumo 1991). Fucoidan has a stronger antithrombotic activity, but a lower anticoagulant activity and hemorrhagic risk than heparin (Durand et al 2008). The mechanisms of action are predominantly on HC-II mediated antithrombin activities, direct antithrombin action (thrombin-fibrinogen complex) and minor AT-III involvements (Shanmugam & Mody 2000).…”

Algal Polysaccharides, Novel Applications and Outlook

“…The presence of abundant 3-O-sulfated glucosamines in Heparan sulfates from human follicular fluid has suggested that some biological activities could be mimicked by other sulfated polysaccharides or derivatives (de Agostini et al, 2008). Low molecular weight fucoidan (LMWF) has been used to demonstrate this (Colliec et al, 1991, Millet et al, 1999and Durand et al, 2008.…”