Compound of aspartic acid with heparin as a tool for thrombogenesis prevention: 612.115.3:612.115.064

Abstract

Summary. Background. Aspartic acid participates in metabolism, promotes the entry of potassium and magnesium ions into the cell, is the neurotransmitter of the central nervous system, exhibits adaptogenic effect and positively affects on the heart muscle. Blood anticoagulant heparin, like aspartic acid, contributes to the regulation of the nervous, endocrine, and immune systems. However, no information was found in the literature about the effect of aspartic acid compounds with heparin on anticoagulant and fibrinolytic blood properties. Objectives: to create a compound of aspartic acid with heparin (AH) and to study its effect on anticoagulant and fibrinolytic blood activity in vitro and in vivo. Materials/Methods. High molecular weight heparin (Serva, USA) and aspartic acid prep- arations (Reahim LLC, Russia) were used in the experiments that were carried out on Wistar male rats (n=38) weighing 250–300 g. The animals were divided into 4 groups: group 1 (n = 10) received AН; group 2 (n = 10) received aspartic acid (A); group 3 (n = 8) received heparin (H); control group 4 consisted of normal healthy animals (n=10) received 0.85% sodium chloride solution instead of drugs. The drugs were administered per os for 5 days every 24 hours. Blood was taken from vena jugularis 20 hours after the fifth (last) drugs administration and 7 days (168 hours) after canceling their introduction. In vitro, the total (TFA), enzymatic (EFA) and non-enzy- matic (fibrin-depolymerization, FDPA) fibrinolytic activities of the AH compound within concentration range from 10–2 to 10–6 M were determined, as well as anticoagulant activity according to the tests of activated partial thromboplastin time (APTT) and thrombin time (TT) when each of the drugs (compound AH, A, H) was added to plasma of healthy animals. In vivo, 20 and 168 hours after the fifth drugs administration, fibrinolysis (according TFA, EFA, FDPA), tissue plasminogen activator (TPA) activity, anticoagulant activity (according to APTT and TT) were determined in blood plasma of all animals. Results. In vitro AH compound had high anticoagulant and fibrin-depolymerization activities and inhibited thrombin activity compared to its constituent parts. In vivo 20 hours after the last administration, AH compound increased anticoagulant activity (according to APTT and TT) by 24%, fibrinolytic activity (according to TFA, EFA, FDPA and TAP) by 106, 70, 180 and 37%, respectively and promoted the inhibition of fibrin polymerization processes compared to constituent parts of AH compound. A similar pattern was identified 168 hours after AH compound administration, in contrast to its constituent parts: anticoagulant activity (according to APTT) was significantly (by 22%) prolonged, TFA, FDPA, and EFA also remained elevated (by 55–61 and 100%, respectively), that testified the duration of AH compound effects. Conclusions. The duration of the anti- coagulant effect of the studied AH compound was proved. The possible action mechanisms of AH compound in blood flow due to the properties of both the new compound as well as heparin included, have been considered. The use of drugs containing aspartic acid and heparin is promising to prevent thrombogenesis, which is often observed in coronary heart disease.

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