A Non-Anticoagulant Heterofucan has Antithrombotic Activity in vivo

Abstract

Fucan is a term used to denominate a family of sulfated L-fucose-rich polysaccharides. The brown alga Spatoglossum schröederi (Dictyotaceae) has three heterofucans namely fucan A, B and C. The 21 kDa fucan A is composed of a core of a β (1 - 3) glucuronic acid-containing oligosaccharide of 4.5 kDa with branches at C4 of the fucose chains α (1 - 3) linked. The fucose is mostly substituted at C4 with a sulfate group and at C2 with chains of β (1 - 4) xylose. This fucan has neither anticoagulant (from from 0.1 to 100 μg) nor hemorrhagic activities (from 50 to 800 μg/mL). The antithrombotic test in vivo showed that fucan A has no activity in any of the concentrations (from 0.2 to 20 μg/g/day) tested 1 h after polysaccharide administration. However, when fucan A was injected endovenously 24 h before the ligature of the venae cavae, we observed a dose-dependent effect, reaching saturation at around 20 μg/g of rat weight. In addition, this effect is also time-dependent, reaching saturation around 16 h after fucan administration. In addition, regardless of the administration route, fucan A displayed antithrombotic activity. The exception was the oral pathway. Of particular importance was the finding that fucan A stimulates the synthesis of an antithrombotic heparan sulfate from endothelial cells like heparin. The hypothesis has been raised that the in vivo antithrombotic activity of fucan A is related to the increased production of this heparan. Taken together with the fact that the compound is practically devoid of anticoagulant and hemorrhagic activity, the data suggest that it may be an ideal antithrombotic agent in vivo.

Abbreviations

APTT: activated partial thromboplastin time

CS: chondroitin sulfate

FUC: fucoidan from Fucus vesiculosus

FUC A: fucan A from Spatoglossum schröederi

HEP: heparin

HS: heparin sulfate

PRP: platelet-rich plasma

PPP: platelet-poor plasma

PT: protrombin time

TT: thrombin time

Key words

Brown algae - fucoidan - anticoagulant drugs - antithrombotic agents - Dictyotaceae - Spatoglossum schröederi

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