Antithrombin and heparin cofactor II-mediated inactivation of alpha-thrombin by a synthetic, sulfated mannogalactan

作者：Gracher Ana Helena P; Cipriani Thales R; Carbonero Elaine R; Gorin Philip A J; Iacomini Marcello^*

来源：Thrombosis Research, 2010, 126(3): E180-E187.

DOI：10.1016/j.thromres.2010.04.008

• Sulfated polysaccharide
• Mannogalactan
• Pleurotus ostreatoroseus
• Antithrombotic
• Antithrombin
• Heparin cofactor II

Introduction: A mannogalactan from Pleurotus ostreatoroseus (MgPr) was chemically sulfated to give MgPr-S1, which was evaluated for its anticoagulant and antithrombotic activities, bleeding tendency, and platelet aggregation.
Materials and methods: MgPr-S1 was partially characterized by HPSEC-MALLS, methylation analysis, and (13)C NMR spectroscopy. Its anticoagulant activity was determined by assays of aPTT, TT, alpha-thrombin and factor Xa residual activity, heparin cofactor II (HCII)-, or antithrombin (AT)-mediated inhibition. The antithrombotic effect was evaluated in rats using a venous thrombosis model and the bleeding tendency was also tested in vivo. Platelet aggregation was investigated by an adaptation of the method of Born [1].
Results: The hydroxyl groups of beta-D-Manp units and OH-2 and OH-4 of the (1 -> 6)-linked alpha-D-Galp units were preferentially substituted. The anticoagulant activity of MgPr-S1 was mainly by thrombin inhibition with antithrombin and HCII, and had an effect on platelet aggregation induced by ADP and alpha-thrombin. It almost completely inhibited thrombus formation in vivo at a dose of 6 mg/kg and heparin inhibited thrombus formation at a dose of 0.200 mg/kg.
Conclusions: These results suggested that the chemically sulfated mannogalactan could act as an alternative to heparin as anticoagulant.

• 出版日期2010-9