The effect of phosphorylated hesperidin on the polymerization of fibrinogen as studied by light scattering.

In previous publications from this laboratory (1, 2), it was demonstrated that phosphorylated hesperidin acted as a potent anticoagulant when administered intravenously to rabbits. The mode of action of this material appeared to be similar to that of heparin, since only the plasma recalcification times and antithrombin titers showed significant changes, whereas the prothrombin times, antithromboplastin titers, and serum calcium levels were within the normal range. Also the injection of protamine nullified the hypocoagulability of blood produced by phosphorylated hesperidin. Beiler and Martin (3) have shown that phosphorylated and sulfonated hesperidins and to a lesser degree the acetylated derivative are hyaluronidase inhibitors. Heparin likewise possesses antihyaluronidase activity (4), but this property is less utilized bhan it,s anticoagulant action. However, when heparin is desulfated both these properties are destroyed (4). In the presence of blood, the anticoagulant action of heparin is due to its combination with a heparin cofactor to form an antithrombin (5) which blocks the fibrinogen activation step in the blood coagulation mechanism. On the other hand, the anticoagulant property of heparin acting on a fibrinogenthrombin system in vitro has been attributed to its high negative surface charge (6) which provides sufficient repulsive forces in the polymerizing environment to hinder both the activation and the association of fibrinogen molecules. It was reasoned that if the anticoagulant and antihyaluronidase properties of heparin xyere due to electrostatic interaction with neighboring charged particles, then perhaps the same mechanism could account for the anticoagulant properties of the highly charged phosphorylated hesperidin. In this paper are reported the results of an investigation of the action of phosphorylated hesperidin on the thrombin-induced conversion of fibrinogen studied by the light scattering technique as a function of ionic strength,