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

• Published in: Thrombosis and haemostasis Vol. 101; no. 5; p. 860
• Main Authors: Cipriani, Thales R, Gracher, Ana Helena P, de Souza, Lauro M, Fonseca, Roberto J C, Belmiro, Celso L R, Gorin, Philip A J, Sassaki, Guilherme L, Iacomini, Marcello
• Format: Journal Article
• Language: English
• Published: Germany 01.05.2009
• Subjects: Animals; Anticoagulants - chemistry; Anticoagulants - isolation & purification; Anticoagulants - pharmacology; Anticoagulants - toxicity; Blood Coagulation - drug effects; Citrus sinensis - chemistry; Disease Models, Animal; Dose-Response Relationship, Drug; Factor Xa Inhibitors; Female; Fibrinolytic Agents - chemistry; Fibrinolytic Agents - isolation & purification; Fibrinolytic Agents - pharmacology; Fibrinolytic Agents - toxicity; Hemorrhage - chemically induced; Humans; Male; Molecular Weight; Pectins - chemistry; Pectins - isolation & purification; Pectins - pharmacology; Pectins - toxicity; Platelet Aggregation - drug effects; Rats; Rats, Wistar; Structure-Activity Relationship; Sulfates - chemistry; Sulfates - isolation & purification; Sulfates - pharmacology; Sulfates - toxicity; Thrombin - antagonists & inhibitors; Venous Thrombosis - blood; Venous Thrombosis - prevention & control
• ISSN: 0340-6245; 2567-689X
• DOI: 10.1160/TH08-08-0556

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 alpha-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 antithrombotic 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 alpha-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.