Contributions
Abstract: PB2203
Type: Publication Only
Background
Previously, it was established that proline- and glycine-containing peptides have fibrinolytic, anticoagulant activity, inhibit platelet aggregation and thrombin activity in vitro and in vivo. Besides, it is known that short peptides of this family also have antithrombotic effects.
Aims
To study the influence of Pro-Gly-Pro-Leu (PGPL) and amino-acid leucine on fibrinolytic and anticoagulant blood activity, platelet aggregation and to estimate their possibility to reduce the formation of experimental blood clots .
Methods
Experiments were carried out on white rats (200-250 g) according to the ethical principles of the Helsinki Declaration. Peptide PGPL (1 mg/kg), leucine (0.33 mg/kg - equivalent to its content in PGPL) and saline (control rats) were intranasal entered to rats within 3 days. 1 hour after the last drugs administration we induced the formation of thrombus in v.jugularis (Wessler model). The degree of thrombus formation was estimated on thrombus weight. Fibrinolytic activity and activity of tissue-plasminogen activator (t-PA) of blood plasma were measured by fibrin plate method. Anticoagulant activity (APTT-test) and ADP-induced platelet aggregation were detected by standard methods.
Results
Our experiments demonstrated that preliminary intranasal administration of PGPL (before formation of thrombus) leads to increase of APTT, fibrinolytic and t-PA activity on 18%, 62%, 35% accordingly from control rats. Besides, we observed the decrease of platelet aggregation. Also we indicated the reduction of thrombus weigh in PGPL-treated rats on 68.5% comparatively with control rats. The thrombus weigh after leucine treatment decreased on 30% compared with control rats. But administration of leucine did not change of haemostasis system parameters.
Conclusion
Thus administration of PGPL enhanced of anticoagulant, fibrinolytic and antiplatelet activity in rats blood plasma. PGPL pretreatment lead to prevention of experimental venous thrombus formation. Therefore, PGPL may be used as perspective anticoagulant and fibrinolytic agent with direct antithrombotic effect.
Session topic: 34. Thrombosis and vascular biology
Keyword(s): Thrombosis, Peptide, Antithrombotic Therapy, Animal model
Abstract: PB2203
Type: Publication Only
Background
Previously, it was established that proline- and glycine-containing peptides have fibrinolytic, anticoagulant activity, inhibit platelet aggregation and thrombin activity in vitro and in vivo. Besides, it is known that short peptides of this family also have antithrombotic effects.
Aims
To study the influence of Pro-Gly-Pro-Leu (PGPL) and amino-acid leucine on fibrinolytic and anticoagulant blood activity, platelet aggregation and to estimate their possibility to reduce the formation of experimental blood clots .
Methods
Experiments were carried out on white rats (200-250 g) according to the ethical principles of the Helsinki Declaration. Peptide PGPL (1 mg/kg), leucine (0.33 mg/kg - equivalent to its content in PGPL) and saline (control rats) were intranasal entered to rats within 3 days. 1 hour after the last drugs administration we induced the formation of thrombus in v.jugularis (Wessler model). The degree of thrombus formation was estimated on thrombus weight. Fibrinolytic activity and activity of tissue-plasminogen activator (t-PA) of blood plasma were measured by fibrin plate method. Anticoagulant activity (APTT-test) and ADP-induced platelet aggregation were detected by standard methods.
Results
Our experiments demonstrated that preliminary intranasal administration of PGPL (before formation of thrombus) leads to increase of APTT, fibrinolytic and t-PA activity on 18%, 62%, 35% accordingly from control rats. Besides, we observed the decrease of platelet aggregation. Also we indicated the reduction of thrombus weigh in PGPL-treated rats on 68.5% comparatively with control rats. The thrombus weigh after leucine treatment decreased on 30% compared with control rats. But administration of leucine did not change of haemostasis system parameters.
Conclusion
Thus administration of PGPL enhanced of anticoagulant, fibrinolytic and antiplatelet activity in rats blood plasma. PGPL pretreatment lead to prevention of experimental venous thrombus formation. Therefore, PGPL may be used as perspective anticoagulant and fibrinolytic agent with direct antithrombotic effect.
Session topic: 34. Thrombosis and vascular biology
Keyword(s): Thrombosis, Peptide, Antithrombotic Therapy, Animal model