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Thromb Haemost 2001; 86(06): 1540-1546
DOI: 10.1055/s-0037-1616760
Review Article
Schattauer GmbH

Dual Effects of Sulfated D-galactans from the Red Algae Botryocladia occidentalis Preventing Thrombosis and Inducing Platelet Aggregation

Wladimir R. L. Farias
1   Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Departamento de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
2   Departamento de Engenharia de Pesca, Universidade Federal do Ceará, Fortaleza, Ceará, Brazil
,
Rômulo A. Nazareth
1   Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Departamento de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
,
Paulo A. S. Mourão
1   Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho and Departamento de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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Publikationsverlauf

Received 15. Februar 2001

Accepted after revision 26. Juni 2001

Publikationsdatum:
12. Dezember 2017 (online)

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Summary

Sulfated D-galactans occur on the red algae Botryocladia occidentalis as three fractions that differ in their sulfate content. Fractions F2 and F3 are potent anticoagulants. Like heparin, they enhance thrombin and factor Xa inhibition by antithrombin and/or heparin cofactor II. The inhibition potency increases simultaneously with the sulfate content of the fractions. The antithrombotic activity of these sulfated D-galactans was investigated on an experimental thrombosis model in which thrombus formation was induced by a combination of stasis and hypercoagulability. In contrast with heparin, the sulfated D-galactans showed a dual dose-response curve preventing thrombosis at doses up to0.5 mg/ kg body weight but losing the effect at higher doses. This unexpected behavior is probably due to a combined action of the sulfated D-galactan as anticoagulant and also as a strong inducer of platelet aggregation. In platelet-depleted animals the antithrombotic activity at higher dose of sulfated D-galactan is restored and almost total inhibition of thrombus formation is achieved. The sulfated D-galactan has no hemorrhagic effect even at high doses, possibly as a consequence of its effect on platelet aggregation. At comparable dose heparin has an intense bleeding effect. These results indicate that new polysaccharides, with well-defined structures, can help to distinguish events, such as antithrombotic and anticoagulant activities, bleeding and platelet-aggregating effects, which are obscure when induced simultaneously by a single compound.

Keywords

Sulfated galactan - antithrombotic action - anticoagulant activity - algal polysaccharide - platelet aggugation
 

  • References

  • 1 Albano RM, Mourão PAS. Isolation, fractionation, and preliminary characterization of a novel class of sulfated glycans from the tunic of Styela plicata (Chordata, Tunicata). J Biol Chem 1986; 261: 758-65.
    PubMedGoogle Scholar
  • 2 Mourão PAS, Perlin AS. Structural features of sulfated glycans from the tunic of Styela plicata (Chordata-Tunicata): a unique occurrence of L-galactose in sulfated polysaccharides. Eur J Biochem 1987; 166: 431-36.
    CrossrefPubMedGoogle Scholar
  • 3 Mourão PAS, Bastos IG. Highly acidic glycans from sea cucumbers: isolation and fractionation of fucose-rich sulfated polysaccharides from the body wall of Ludwigothurea grisea . Eur J Biochem 1987; 166: 639-45.
    CrossrefPubMedGoogle Scholar
  • 4 Vieira RP, Mourão PAS. Occurrence of a unique fucose-branched chondroitin sulfate in the body wall of a sea cucumber. J Biol Chem 1988; 263: 18176-83.
    PubMedGoogle Scholar
  • 5 Pavão MSG, Albano RM, Lawson AM, Mourão PAS. Structural heterogeneity among unique sulfated L-galactans from different species of ascidians (Tunicates). J Biol Chem 1989; 264: 9972-79.
    PubMedGoogle Scholar
  • 6 Vieira RP, Mulloy B, Mourão PAS. Structure of a fucose-branched chondroitin sulfate from sea cucumber: evidence for the presence of 3-O-sulfo-β-D-glucuronosyl residues. J Biol Chem 1991; 266: 13530-6.
    PubMedGoogle Scholar
  • 7 Santos JA, Mulloy B, Mourão PAS. Structural diversity among sulfated α-L-galactans from ascidians (tunicates): studies on the species Ciona intestinalis and Herdmania monus . Eur J Biochem 1992; 204: 669-77.
    CrossrefPubMedGoogle Scholar
  • 8 Mulloy B, Ribeiro AC, Alves AP, Vieira RP, Mourão PAS. Sulfated fucans from echinoderms have a regular tetrasaccharide repeating unit defined by specific patterns of sulfation at the O-2 and O-4 positions. J Biol Chem 1994; 269: 22113-23.
    PubMedGoogle Scholar
  • 9 Pavão MSG, Mourão PAS, Mulloy B, Tollefsen DM. A unique dermatan sulfate-like glycosaminoglycan from ascidian: its structure and the effect of its unusual sulfation pattern on coagulation activity. J Biol Chem 1995; 270: 31027-36.
    CrossrefPubMedGoogle Scholar
  • 10 Alves AP, Mulloy B, Diniz JA, Mourão PAS. Sulfated polysaccharides from the egg jelly layer are species-specific inducers of acrosomal reaction in sperms of sea urchins. J Biol Chem 1997; 272: 6965-71.
    CrossrefPubMedGoogle Scholar
  • 11 Alves AP, Mulloy B, Moy GW, Vacquier VD, Mourão PAS. Females of the sea urchin Strongylocentrotus purpuratus differ in the structure of their egg jelly sulfated fucans. Glycobiology 1998; 8: 939-46.
    CrossrefPubMedGoogle Scholar
  • 12 Vilela-Silva ACES, Alves AP, Valente AP, Vacquier VD, Mourão PAS. Structure of the sulfated -L-fucan from the egg jelly coat of the sea urchin Strongylocentrotus franciscanus: patterns of preferential 2-O- and 4-O-sulfation determine sperm cell recognition. Glycobiology 1999; 9: 927-33.
    CrossrefPubMedGoogle Scholar
  • 13 Mourão PAS, Pereira MS, Pavão MSG, Mulloy B, Tollefsen DM, Mowinckel MC, Abildgaard U. Structure and anticoagulant activity of a fucosylated chondroitin sulfate from echinoderm: sulfated fucose branches on the polysaccharide account for its high anticoagulant action. J Biol Chem 1996; 271: 23973-84.
    CrossrefPubMedGoogle Scholar
  • 14 Pavão MSG, Aiello KRM, Werneck CC, Silva LCF, Valente AP, Mulloy B, Colwell NS, Tollefsen DM, Mourão PAS. Highly sulfated dermatan sulfate from ascidians: structure versus anticoagulant activity of these glycosaminoglycans. J Biol Chem 1998; 273: 27848-57.
    CrossrefPubMedGoogle Scholar
  • 15 Mourão PAS, Guimarães MAM, Mulloy B, Thomas S, Gray E. Antithrombotic activity of a fucosylated chondroitin sulfate from echinoderm: sulphated fucose branches on the polysaccharide account for its antithrombotic action. Brit J Haematol 1998; 101: 647-52.
    CrossrefPubMedGoogle Scholar
  • 16 Pacheco RG, Vicente CP, Zancan P, Mourão PAS. Different antithrombotic mechanisms among glycosaminoglycans revealed with a new fucosylated chondroitin sulfate from echinoderm. Blood Coag Fibrinol 2000; 11: 563-73.
    CrossrefPubMedGoogle Scholar
  • 17 Pereira MS, Mulloy B, Mourão PAS. Structure and anticoagulant activity of sulfated fucans: comparison between the regular, repetitive, and linear fucans from echinoderms with the more heterogeneous and branched polymers from brown algae. J Biol Chem 1999; 274: 7656-67.
    CrossrefPubMedGoogle Scholar
  • 18 Farias WRL, Valente AP, Pereira MS, Mourão PAS. Structure and anticoagulant activity of sulfated galactans. Isolation of a unique sulfated galactan from the red algae Botryocladia occidentalis and comparison of its anticoagulant action with that of sulfated galactans from invertebrates. J Biol Chem 2000; 275: 29299-307.
    CrossrefPubMedGoogle Scholar
  • 19 Farndale RW, Buttle DJ, Barret AJ. Improved quantitation and discrimination of sulfated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta 1986; 883: 173-77.
    CrossrefPubMedGoogle Scholar
  • 20 Dubois M, Gilles KA, Hamilton JK, Rebers PA, Smith F. Colorimetric method for determination of sugars and related substance. Anal Chem 1956; 28: 350-4.
    CrossrefPubMedGoogle Scholar
  • 21 Anderson LO, Barrowcliffe TW, Holmer E, Johnson EA, Sims GEC. Anticoagulant properties of heparin fractionated by affinity chromatography on matrix-bound antithrombin-3 and by gel-filtration. Thromb Res 1976; 9: 575-80.
    CrossrefPubMedGoogle Scholar
  • 22 Teien AN, Abildgaard U, Hook M. Anticoagulant effect of heparan sulfate and dermatan sulfate. Thromb Res 1976; 8: 859-67.
    CrossrefPubMedGoogle Scholar
  • 23 Abildgaard U, Larsen ML. Assay of dermatan sulfate cofactor (Heparin-cofactor II) activity in human-plasma. Thromb Res 1984; 35: 257-66.
    CrossrefPubMedGoogle Scholar
  • 24 Vogel GM, Meuleman DG, Bourgondiën FG, Hobbelen M. Comparison of two experimental thrombosis models in rats: effect of four glycosaminogly-cans. Thromb Res 1989; 54: 399-410.
    CrossrefPubMedGoogle Scholar
  • 25 Herbert JM, Héralt JP, Bernat A, Van Amsterdam RGM, Vogel GMT, Lormeau JC, Petitou M, Meuleman DG. Biochemical and pharmacological properties of SANORG 32701. Comparison with the “synthetic pentasaccharide (SR 90107/org 31540)” and standard heparin. Circ Res 1996; 79: 590-600.
    CrossrefPubMedGoogle Scholar
  • 26 Saito H, Yamagata T, Suzuki S. Enzymatic methods for the determination of small quantities of isomeric chondroitin sulfates. J Biol Chem 1968; 245: 1536-42.
    PubMedGoogle Scholar
  • 27 Maeda M, Uehara T, Harada N, Sekiguchi M, Hiraoka A. Heparinoide-active sulphated polysaccharides from Monostroma nitidum and their distribution in the chlorophyta. Phytochemistry 1991; 30: 3611-14.
    CrossrefPubMedGoogle Scholar
  • 28 Rogers DJ, Iurd KM, Blunden G, Paoletti S, Zanetti F. Anticoagulant activity of a proteoglycan in extracts of Codium fragile ssp. atlanticum. J Applied Physiol 1990; 2: 357-61.
    PubMedGoogle Scholar
  • 29 Potin P, Patier P, Jean-Ives F, Jean-Claude Y, Rochas C, Kloareg B. Chemical characterization of cell-wall polysaccharides from tank-cultivated and wild plants of Delesseria sanguinea (Hudson) Lamouroux (Ceramiales-Delesseriaceae): culture patterns and potent anticoagulant activity. J Applied Physiol 1992; 4: 119-28.
    PubMedGoogle Scholar
  • 30 Sem SR, Das AK, Banerji N, Siddhanta AK, Mody KH, Ramavat BK, Chauhan VD, Vedasiromani JR, Ganguly DK. A new sulfated polysaccha-ride with potent blood anticoagulant activity from the red seaweed Grateloupia indica . Int J Biol Macromol 1994; 16: 279-80.
    CrossrefPubMedGoogle Scholar
  • 31 Kolender AA, Pujol CA, Damonte EB, Matulewicz MC, Cerezo AS. The system of sulfated α-(1→3) linked D-mannans from the red seaweed Nothogenia fastigiate: structures, antiherpetic and anticoagulant properties. Carbohydr Res 1997; 304: 53-60.
    CrossrefPubMedGoogle Scholar
  • 32 Grauffel V, Kloareg B, Mabeau S, Durand P, Jozefonvicz J. New natural polysaccharides with potent antithrombotic activity: fucans from brown algae. Biomaterials 1989; 10: 363-8.
    CrossrefPubMedGoogle Scholar
  • 33 Nishino T, Aizu Y, Nagumo T. Antithrombin activity of a fucan sulfate from the brown seaweed Acklonia kurome . Thromb Res 1991; 62: 765-73.
    CrossrefPubMedGoogle Scholar
  • 34 Church FC, Meade JB, Treanor RE, Whinna HC. Antithrombin activity of fucoidan. The interaction of fucoidan with heparin cofactor II, antithrombin III, and thrombin. J Biol Chem 1989; 264: 3618-23.
    PubMedGoogle Scholar
  • 35 Colliec-Jouault S, Fisher AM, Tapon-Bretaudière J, Boisson C, Jazefonvicz J. Anticoagulant properties of a fucoidan fraction. Thromb Res 1991; 64: 143-54.
    CrossrefPubMedGoogle Scholar
  • 36 Colliec S, Boisson-Vidal C, Jozefonvicz J. A low molecular weight fucoidan from the brown seaweed Pelvetia canaliculata . Phytochemistry 1994; 35: 697-700.
    CrossrefPubMedGoogle Scholar
  • 37 Herbert JM, Bernat A, Maffrand JP. Importance of platelets in experimental venous thrombosis in the rat. Blood 1992; 80: 2281-6.
    PubMedGoogle Scholar
  • 38 Davie EW, Fujikawa K, Kisiel W. The coagulation cascade: initiation, maintenance and regulation. Biochemistry 1991; 30: 10363-70.
    CrossrefPubMedGoogle Scholar
  • 39 Warkentin TE. Heparin-induced thrombocytopenia: a clinicopathologic syndrome. Thromb Haemost 1999; 82: 439-47.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 40 Visentin GP. Heparin-induced thrombocytopenia: molecular pathogenesis. Thromb Haemost 1999; 82: 448-56.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 41 Hirsh J. Heparin induced bleeding. Nouv Rev Franç Hematol 1984; 26: 261-6.
    PubMedGoogle Scholar
  • 42 Arthur UK, Isbister JP, Aspery EM. The heparin induced thrombosisthrombocitopenia syndrome (HITTS): a review. Pathology 1985; 16: 82-6.
    PubMedGoogle Scholar
  • 43 Doutremepuich C, Azougagh Oualane F, Doutremepuich F, Fareed J. New class of heparin derivatives with a potent antithrombotic effect and a very limited hemorrhagic activity. Thromb Res 1996; 83: 217-28.
    CrossrefPubMedGoogle Scholar
  • 44 Thomas DP. Does low molecular weight heparin cause less bleeding?. Thromb Haemost 1997; 78: 1422-5.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 45 Hirsh J, Raschke R, Warkentin TE, Dalen JE, Deykin D, Poller L. Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficay, and safety. Chest 1995; 108: 258S-275S.
    CrossrefPubMedGoogle Scholar
  • 46 Hirsh J, Dalen JE, Deykin D, Poller L, Bussey H. Oral anticoagulants. Mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 1995; 108: 231S-246S.
    CrossrefPubMedGoogle Scholar