Influence of molecular weight of chemically sulfated citrus pectin fractions on their antithrombotic and bleeding effects

Thales R. Cipriani; Ana Helena P. Gracher; Lauro M. de Souza; Roberto J. C. Fonseca; Celso L. R. Belmiro; Philip A. J. Gorin; Guilherme L. Sassaki; Marcello Iacomini

doi:10.1160/TH08-08-0556

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 101(05): 860-866
DOI: 10.1160/TH08-08-0556

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Influence of molecular weight of chemically sulfated citrus pectin fractions on their antithrombotic and bleeding effects

Thales R. Cipriani

¹Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil

,

Ana Helena P. Gracher

¹Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil

,

Lauro M. de Souza

¹Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil

,

Roberto J. C. Fonseca

²Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

Celso L. R. Belmiro

²Laboratório de Tecido Conjuntivo, Hospital Universitário Clementino Fraga Filho, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

,

Philip A. J. Gorin

¹Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil

,

Guilherme L. Sassaki

¹Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil

,

Marcello Iacomini

¹Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil

› Author Affiliations

Abstract

Summary

Evaluated were the anticoagulant and antithrombotic activities, and bleeding effect of two chemically sulfated polysaccharides, obtained from citric pectin, with different average molar masses. Both low-molecular-weight (Pec-LWS, 3,600 g/mol) and high-molecular-weight sulfated pectins (Pec-HWS, 12,000 g/mol) had essentially the same structure, consisting of a (1→4)-linked α-D-GalpA chain with almost all its HO-2 and HO-3 groups substituted by sulfate. Both polysaccharides had anticoagulant activity in vitro, although Pec-HWS was a more potent anti-thrombotic agent in vivo, giving rise to total inhibition of venous thrombosis at a dose of 3.5 mg/kg body weight. Surprisingly, in contrast with heparin, Pec-HWS and Pec-LWS are able to directly inhibit α-thrombin and factor Xa by a mechanism independent of antithrombin (AT) and/or heparin co-factor II (HCII). Moreover, Pec-HWS provided a lower risk of bleeding than heparin at a dose of 100% effectiveness against venous thrombosis, indicating it to be a promising antithrombotic agent.

Keywords

Sulfated polysaccharide - citrus pectin - anticoagulant - antithrombotic

Full Text

References

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