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Published on: January 22, 2015
Antithrombotic and anticomplementary properties of a very low molecular mass dermatan sulfate
María Fabiana Alberto1, Diego Giaquinta Romero, María Lazzari
1Academia Nacional de Medicina, Avenida Las Heras 3092, (C1425AUM) Ciudad Autónoma de Buenos Aires, Argentina.
Introduction:
Dermatan sulfate, a sulfated glycosaminoglycan, acts as an anticoagulant by accelerating the inhibition of thrombin by heparin cofactor II.
Materials And Methods:
A low molecular mass dermatan sulfate was obtained by peroxy-radical depolymerization from a parent dermatan sulfate. Chemical characterization of this low molecular mass dermatan sulfate shows a material of approximately 5 kDa that conserves sulfated sequences (2-O-sulfation of the iduronic acid units and/or 4 or 6 positions of galactosamina N acetyl) essential for dermatan sulfate-heparin cofactor II interaction with more sulphated proportion (27.7+/-1.9 microg% vs 11.5+/-0.8 microg%, P<0.05 n=6, low molecular mass dermatan sulfate vs dermatan sulfate).
Results:
After a single intravenous administration of low molecular dermatan sulfate in rats, fibrinolytic activity increased simultaneously with thrombin clotting time prolongation. Low molecular dermatan sulfate showed an inhibitory effect on classical complement activation pathway reaching a maximum during the first hour. Furthermore, low molecular dermatan sulfate was as effective as dermatan sulfate to prevent thrombus formation and to diminish thrombus weight in a rat venous thrombosis model.
Conclusions:
The results indicate that peroxy-radical depolymerization of dermatan sulfate produced a low molecular dermatan sulfate with profibrinolytic, thrombolytic, antithrombotic and anticomplement properties. We conclude that low molecular dermatan sulfate may be an effective adjunct in the management of thrombotic events.
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