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Bulletin of Experimental Biology and Medicine, Vol. 147, No. 3, 2009 PHARMACOLOGY AND TOXICOLOGY
Anticoagulant Effects of a Complex of High Molecular Weight Heparin and Arginine
L. A. Lyapina, T. Yu. Obergan, and V. E. Pastorova
Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 147, No. 3, pp. 300-302, March, 2009 Original article submitted October 29, 2008
Heparin forms a complex compound with arginine in a pure system, which was shown by biochemical methods. A method for obtaining the complex in vitro has been developed. At arginine/heparin molar ratio of 3:1 the complex exhibited anticoagulant, antiplatelet, and fibrin-depolymerization activities. High fibrin-depolymerization and anticoagulant activities were documented in the blood of animals 10 min after intravenous injection of the arginine-heparin complex, in contrast to the picture after injection of the complex components (heparin and arginine) alone.
Key Words: arginine-heparin complex; anticoagulant activity; fibrin depolymerization characteristics; platelet aggregation
It was shown previously that arginine (half-substituted amino acid) promotes a reduction of high cholesterol level, normalization of sugar level in the blood, and stimulates wound healing [1,4,9,14]. Arginine improves the blood rheology and prevents thrombogenesis [11,13]. Arginine inhibition of blood clotting is due to the fact that it is a precursor of NO [8], produced by vascular endothelial cells and involved in the functioning of many body systems, including hemostasis [12]. One of the natural anticoagulants of the hemostasis system, heparin, blocks the clotting activity of thrombin [6] and in parallel with this, exhibits hypolipidemic, hypoglycemic, and antiinflammatory effects. Experimental data, confirmed clinically, indicate amplification of the anticoagulant and antidiabetogenic effects of heparin complexes with some low molecular-weight substances [3,5,10].
The aim of our study was to create an anticoagulant heparin-arginine compound and to study its effects on fibrin polymerization, anticoagulant and antiplatelet activities in circulating blood in vivo.
MATERIALS AND METHODS
High molecular weight heparin (Serva) and L-argi-nine preparation were used in the study.
Arginine-heparin complex (molar ratio 3:1) was obtained by our method.
Interactions between arginine guanido groups and heparin acid groups were proven by cross electrophoresis. Total and nonenzymatic fibrinolytic (fibrin depolymerization) activities of the compound were evaluated in vitro for the concentrations of 107-101 mg/ml. Anticoagulant activity and platelet...