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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
1   Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil
,
Ana Helena P. Gracher
1   Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil
,
Lauro M. de Souza
1   Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil
,
Roberto J. C. Fonseca
2   Laboratório 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
2   Laboratório 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
1   Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil
,
Guilherme L. Sassaki
1   Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil
,
Marcello Iacomini
1   Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, Curitiba, Paraná, Brazil
› Author AffiliationsFinancial support: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação Araucária and PRONEX-Carboidratos.
Further Information

Publication History

Received: 01 September 2008

Accepted after major revision: 17 February 2009

Publication Date:
24 November 2017 (online)

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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
 

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