Abstract
Here we study the gemostatic properties of leucine-containing regulatory oligopeptides Н-Pro-Leu-Pro-OH (PLP) and H-Pro-Leu-Pro-Ala-OH (PLPA) administered orally every 24 hours for 7 days to healthy animals (rats). Standard coagulologic techniques were applied. We demonstrated that 20 hours after the 7th administration of the peptides the anticoagulant activity in the blood plasma was increased by 10.3-30.6% according to the activated partial thromboplastin time data, all types of the fibrinolytic process — total plasma fibrinolytic activity by 16-24%, non-enzymatic fibrinolysis – by 9-11%, enzymatic fibrinolysis – by 28-49%, and the plasmin activity – by 29%. In contrast, the lysis time of the euglobulin fibrin clot (in absence of fibrinolysis inhibitors) was not affected. The activity of tissue plasminogen activator was either unchanged (PLP) or decreased under the effect of PLPA. The fibrinogen concentration either decreased by 18% (PLP), or remained at normal values (PLPA); the activity of factor XIIIa decreased by 17% (PLP) and 10% (PLPA). Both peptides suppressed the platelet aggregation by 31-33.5% (when used as an ADP inductor). The most prominent anticoagulant effect was observerd for the oligopeptide containing the additional alanine residue at the C-terminus. Since both peptided showed varying degrees of complex antiplatelet, anticoagulant, fibrindepolymerization, fibrinolytic activity, and moderate reduction of coagulation factor levels — fibrinogen and factor XIIIa — when administered orally to animals, they can be considered promising antithrombotic agents.
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