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

Laboratório de Química de Carboidratos, Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, CP 19046, CEP 81.531-980, Curitiba, PR, Brazil.
Thrombosis and Haemostasis (Impact Factor: 5.76). 05/2009; 101(5):860-6. DOI: 10.1160/TH08-08-0556
Source: PubMed

ABSTRACT 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.

1 Bookmark
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sulfated polysaccharides are recognized for their broad range of biological activities, including anticoagulant properties. The positions occupied by the sulfate groups are often related to the level of the inherent biological activity. Herein the naturally sulfated galactans, kappa-, iota- and theta-carrageenan, were additionally sulfated by regioselective means. The anticoagulant activity of the resulting samples was then studied using the aPTT in vitro assay. The influence of sulfate regiochemistry on the anticoagulant activity was evaluated. From kappa-carrageenan three rare polysaccharides were synthesized, one of them involved a synthetic route with an amphiphilic polysaccharide intermediate containing pivaloyl groups. Iota- and theta-carrageenan were utilized in a selective C6 sulfation at β-d-Galp units to produce different structures comprising trisulfated diads. All the samples were characterized by NMR (1D and 2D). The resulting aPPT measurements suggested that sulfation at C2 of 3,6-anhydro-α-d-Galp and C6 of β-d-Galp increased the anticoagulant activity.
    Carbohydrate Polymers 01/2013; 91(2):483-91. · 3.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: High methoxy citrus pectin was oxidized by periodic acid to prepare a dialdehyde functionalized material. The effect of various reaction conditions, viz., reaction time, reaction temperature, pH of the medium, periodic acid concentration and solvent composition on the oxidation process was investigated. With an increase in the reaction time, the aldehyde content increased. However, the intrinsic viscosity of the system decreased indicating that degradation takes place simultaneously with oxidation. The amount of aldehyde generated also increased with an increase in reaction temperature and the concentration of periodic acid. Due to the polyanionic behaviour of pectin, greater aldehyde contents were obtained at lower pH. Keeping all other reaction conditions constant, greater aldehyde contents were obtained in water-ethanol system than in pure aqueous medium. Increase in the ethanol content increased the amount of aldehyde generated. FTIR spectra of oxidized pectin systems show a carbonyl peak at 1734cm(-1). They further reveal that partial ionisation ofCOOH groups takes place leading to a peak at 1614cm(-1).
    Carbohydrate polymers. 10/2013; 98(1):1160-5.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Crosslinked hydrogels were developed by in-situ reaction of periodate oxidized pectin (OP) and gelatin. The reaction takes place through the formation of Schiff bases between aldehyde groups of OP and amino groups of gelatin. The effect of various process parameters such as reaction time, reaction temperature, pH of the reaction and composition on the efficacy of the crosslinking was investigated. Field emission scanning electron micrsocopy (FESEM) revealed that homogenous, single phase systems are obtained after the crosslinking of OP and gelatin. The swelling characteristics of the hydrogels were monitored. The equilibrium swelling varies in the range of 195-324% with a variation in the gelatin content (10-40%). Glycerol, when used as a plasticizer, improved the flexibility and the handling characteristics of the crosslinked hydrogels. Plasticized films retained good tensile strengths in the range of 19-48MPa. By proper selection of the reaction conditions, the efficiency of crosslinking can be controlled to obtain the optimum results.
    Carbohydrate polymers. 06/2014; 106:312-8.