title: Influence of fucoidans on hemostatic system.
abstract: Three structurally different fucoidans from the brown seaweeds Saccharina latissima (SL), Fucus vesiculosus (FV), and Cladosiphon okamuranus (CO), two chemically modified fucoidans with a higher degree of sulfation (SL-S, CO-S), and a synthetic totally sulfated octasaccharide (OS), related to fucoidans, were assessed on anticoagulant and antithrombotic activities in different in vitro experiments. The effects were shown to depend on the structural features of the compounds tested. Native fucoidan SL with a degree of sulfation (DS) of 1.3 was found to be the most active sample, fucoidan FV (DS 0.9) demonstrated moderate activity, while the polysaccharide CO (DS 0.4) was inactive in all performed experiments, even at high concentrations. Additional introduction of sulfate groups into fucoidan SL slightly decreased the anticoagulant effect of SL-S, while sulfation of CO, giving rise to the preparation CO-S, increased the activity dramatically. The high level of anticoagulant activity of polysaccharides SL, SL-S, and CO-S was explained by their ability to form ternary complexes with ATIII-Xa and ATIII-IIa, as well as to bind directly to thrombin. Synthetic per-O-sulfated octasaccharide OS showed moderate anticoagulant effect, determined mainly by the interaction of OS with the factor Xa in the presence of ATIII. Comparable tendencies were observed in the antithrombotic properties of the compounds tested.
authors.affiliation: Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prospect 47, 119991 Moscow, Russian Federation. ustnad@gmail.com
authors.forename: Nadezhda E
authors.initials: NE
authors.lastname: Ustyuzhanina
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Ushakova
authors.forename: Ksenia A
authors.initials: KA
authors.lastname: Zyuzina
authors.forename: Maria I
authors.initials: MI
authors.lastname: Bilan
authors.forename: Anna L
authors.initials: AL
authors.lastname: Elizarova
authors.forename: Oksana V
authors.initials: OV
authors.lastname: Somonova
authors.forename: Albina V
authors.initials: AV
authors.lastname: Madzhuga
authors.forename: Vadim B
authors.initials: VB
authors.lastname: Krylov
authors.forename: Marina E
authors.initials: ME
authors.lastname: Preobrazhenskaya
authors.forename: Anatolii I
authors.initials: AI
authors.lastname: Usov
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Kiselevskiy
authors.forename: Nikolay E
authors.initials: NE
authors.lastname: Nifantiev
mesh_terms: D000925:Anticoagulants / Q000737:chemistry / Q000494:pharmacology; D000990:Antithrombin III / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015951:Factor Xa / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000494:pharmacology; D044645:Fucus / Q000737:chemistry; D006490:Hemostatics / Q000737:chemistry* / Q000494:pharmacology*; D011134:Polysaccharides / Q000737:chemistry* / Q000494:pharmacology*; D012624:Seaweed / Q000737:chemistry; D013431:Sulfates / Q000737:chemistry; D013917:Thrombin / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006490:Hemostatics; D011134:Polysaccharides; D013431:Sulfates; D000990:Antithrombin III; C007789:fucoidan; D013917:Thrombin; D015951:Factor Xa