title: Sulfation pattern of citrus pectin and its carboxy-reduced derivatives: influence on anticoagulant and antithrombotic effects.
abstract: Citrus pectin (CP), a polysaccharide composed of [→4)-α-D-GalpA-(1→]n, was submitted to one or four carboxy-reduction cycles, resulting in CP-CR1 and CP-CR4, which had 40% and 2% of GalpA units, respectively. The polysaccharides were chemically sulfated and their anticoagulant and antithrombotic effects determined. Sulfated polysaccharides (CP-S, CP-CR1S and CP-CR4S) had different anticoagulant activities, doubling APTT at concentrations of 28.7, 13.2, and 4.9 μg/ml respectively. CP-CR1S and CP-CR4S also showed antithrombotic activity in vivo with ED50 of 3.01 and 1.70 mg/kg, respectively. Like heparin, they inhibited thrombin by a mechanism dependent on AT and HCII. Their hemorrhagic potential was also similar to that of heparin. According to methylation analysis, 91.1% and 50.2% of 6-O-position in CP-CR4S and CP-CR1S were sulfated, respectively. Therefore, substitution of carboxyl groups by sulfate esters in these polysaccharides increases the anticoagulant and antithrombotic effects.
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Paraná, CEP 81531-980, CP 19046, Curitiba, PR, Brazil.
authors.forename: Nadiezda C
authors.initials: NC
authors.lastname: Maas
authors.forename: Ana Helena P
authors.initials: AH
authors.lastname: Gracher
authors.forename: Guilherme L
authors.initials: GL
authors.lastname: Sassaki
authors.forename: Philip A J
authors.initials: PA
authors.lastname: Gorin
authors.forename: Marcello
authors.initials: M
authors.lastname: Iacomini
authors.forename: Thales R
authors.initials: TR
authors.lastname: Cipriani
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D032084:Citrus sinensis / Q000737:chemistry*; D005260:Female; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008297:Male; D010368:Pectins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011134:Polysaccharides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D011134:Polysaccharides; D010368:Pectins