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

2010; Elsevier BV; Volume: 126; Issue: 3 Linguagem: Inglês

10.1016/j.thromres.2010.04.008

1879-2472

Ana Helena P. Gracher, Thales R. Cipriani, Elaine R. Carbonero, Philip A.J. Gorin, Marcello Iacomini,

Antiplatelet Therapy and Cardiovascular Diseases

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 13C NMR spectroscopy. Its anticoagulant activity was determined by assays of aPTT, TT, α-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 β-D-Manp units and OH-2 and OH-4 of the (1→6)-linked α-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 α-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.