Abstract
Clam heparinoid G2 (60.25 kDa) and its depolymerized derivatives DG1 (24.48 kDa) and DG2 (6.75 kDa) prepared from Coelomactra antiquata have been documented to have excellent fibrinolytic and anticoagulant activity. In this study, to further explore the antithrombotic activity of G2, DG1 and DG2, azure A, sheep plasma, and clot lytic rate assays were used to determine their anticoagulant and thrombolytic activity in vitro. The results indicated that the anticoagulant titer of G2 was approximately 70% that of heparin and the thrombolytic activity of DG2 was greater than G2, DG1, and heparin activities. Moreover, in a carrageenan-induced venous thrombosis model, oral administration of G2 and DG1 each at 20 mg/kg and 40 mg/kg for 7 days significantly reduced blacktail thrombus formation, increased tissue-type plasminogen activator, fibrin degradation products, and D-dimer levels, decreased von Willebrand factor and thromboxane B2 levels, and restored phylum and genus abundance changes of intestinal bacteria. DG2 had no antithrombotic effect. At 20 mg/kg, G2, DG1, and heparin had comparable antithrombotic activities, and DG1 at 40 mg/kg had more muscular antithrombotic activity than G2. Thus, DG1 could be an antithrombotic oral agent owing to its more robust antithrombotic activity and lower molecular weight.
Highlights
Published: 5 January 2022Thromboembolic diseases, such as pulmonary embolism, stroke, and myocardial infarction, are characterized by the formation of blood clots within the veins or arteries in different tissues and the travel and lodging of thrombus
The anti-IIa of clam heparinoids decreased as the molecular weight decreased, whereas DG1 had the maximum anti-Xa activity, about 90% that of low-molecular-weight heparin (LMWH)
Our findings indicate that all clam heparinoids of varying molecular weights have some degree of antithrombotic potential
Summary
Thromboembolic diseases, such as pulmonary embolism, stroke, and myocardial infarction, are characterized by the formation of blood clots within the veins or arteries in different tissues and the travel and lodging of thrombus. They are a global health problem [1]. Heparin treatment has several side effects, including thrombocytopenia and bleeding, in addition to the risk of contamination with pathogenic agents, which limit its application [3]. Marine-derived heparinoids, which possess potent antithrombotic properties in multiple pathways and few side effects, are promising alternatives to heparin [5,6]
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