title: Anticoagulant activity of native and partially degraded glycoglucuronomannan after chemical sulfation.
abstract: Heparin has great clinical importance as anticoagulant and antithrombotic agent. However, because of its risks of causing bleeding and contamination by animal pathogens, several studies aim to obtain alternatives to heparin. In the search for anticoagulant and antithrombotic agents from a non-animal source, a glycoglucuronomannan from the gum exudate of the plant Vochysia thyrsoidea was partially hydrolyzed, and both native and partially degraded polysaccharides were chemically sulfated, yielding VThS and Ph-VThS respectively. Methylation analysis indicated that sulfation occurred preferentially at the O-5 position of arabinose units in the VThS and at the O-6 position of mannose units in Ph-VThS. In vitro aPTT assay showed that VThS and Ph-VThS have anticoagulant activity, which could be controlled by protamine, and ex vivo aPTT assay demonstrated that Ph-VThS is absorbed by subcutaneous route. Like heparin, they were able to inhibit α-thrombin and factor Xa by a serpin-dependent mechanism. In vivo, VThS and Ph-VThS reduced thrombus formation by approximately 50% at a dose of 40 IU/kg, similarly to heparin. The results demonstrated that the chemically sulfated polysaccharides are promising anticoagulant and antithrombotic agents.
authors.affiliation: Department of Biochemistry and Molecular Biology, Sector of Biological Sciences, Federal University of Paraná, CP 19.046, CEP 81.531-980, Curitiba, PR, Brazil.
authors.forename: Helyn Priscila
authors.initials: HP
authors.lastname: de Oliveira Barddal
authors.affiliation: Department of Biochemistry and Molecular Biology, Sector of Biological Sciences, Federal University of Paraná, CP 19.046, CEP 81.531-980, Curitiba, PR, Brazil; Department of Cellular Biology, Sector of Biological Sciences, Federal University of Paraná, CP 19.031, CEP 81.531-980, Curitiba, PR, Brazil.
authors.forename: Ana Helena Pereira
authors.initials: AH
authors.lastname: Gracher
authors.affiliation: Department of Biochemistry and Molecular Biology, Sector of Biological Sciences, Federal University of Paraná, CP 19.046, CEP 81.531-980, Curitiba, PR, Brazil.
authors.forename: Fernanda Fogagnoli
authors.initials: FF
authors.lastname: Simas-Tosin
authors.affiliation: Department of Biochemistry and Molecular Biology, Sector of Biological Sciences, Federal University of Paraná, CP 19.046, CEP 81.531-980, Curitiba, PR, Brazil.
authors.forename: Marcello
authors.initials: M
authors.lastname: Iacomini
authors.affiliation: Department of Biochemistry and Molecular Biology, Sector of Biological Sciences, Federal University of Paraná, CP 19.046, CEP 81.531-980, Curitiba, PR, Brazil. Electronic address: trcipriani@ufpr.br.
authors.forename: Thales Ricardo
authors.initials: TR
authors.lastname: Cipriani
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000737:chemistry* / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000737:chemistry* / Q000494:pharmacology*; D005965:Glucuronates / Q000737:chemistry* / Q000494:pharmacology*; D006031:Glycosylation; D008297:Male; D008358:Mannose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000737:chemistry*
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D005965:Glucuronates; D013431:Sulfates; C578162:glucuronomannan; D008358:Mannose
keywords: Anticoagulant activity; Chemical sulfation; Polysaccharide