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ANTITHROMBOTIC ACTIVITY OF PEPTIDE SELANK AGAINST THE BACKGROUND OF EXPERIMENTALLY INDUCED ENDOTHELIAL DYSFUNCTION IN RATS
Author(s):
Elina Rogozinskaya
Affiliations:
M.V. Lomonosow Moscow State University,Moscow,Russian Federation
(Abstract release date: 05/17/18) EHA Library. Rogozinskaya E. 06/14/18; 216838; PB2522
Elina Rogozinskaya
Elina Rogozinskaya
Contributions
Abstract

Abstract: PB2522

Type: Publication Only

Background
Peptides of a glyproline series, including tripeptides PRO-GLY-PRO (PGP), are formed in the body during the hydrolysis of collagen and elastin. They carry out peptidergic regulation in the body. Multiple studies have shown that glyiprolines are effective and have antiplatelet and anticoagulant properties. Recent experimental data indicate an increase in the effects of glyiprolines when different amino acids are added to the protein structure. Thus, the amino acid arginine ARG (R) increases antithrombotic effects in the body due to the release into the bloodstream of NO.

Aims
Study an influence of arginine-containing peptide Selank on the parameters of the hemostasis system against the background of endothelial dysfunction.

Methods
Endothelial dysfunction was caused by repeated administration of a solution of NO-synthase inhibitor - L-name at a concentration of 10 mg/kg. As the drug, Selank peptide THR-LYS-PRO-ARG-PRO-GLY-PRO (TKPRPGP) was intranasal used at a concentration of 100 μg/kg. All animal experiments were conducted in accordance with ethical principles and documents of the European Convention for the Protection of Vertebrates. White Wistar rats (300 g) were divided into 4 groups: 3 test groups (rats receiving Selank; L-name; Selank + L-name); 1 group - control (NaCl). The substances were administered for 7 days daily every 24 hours. On the 8th day, blood was taken from the jugular vein and a series of experiments was conducted to determine the effect of drugs on the parameters of hemostasis. After the cancellation of Selank, but the continued introduction of L-name, after 7 days, a series of experiments were repeated. The studies were performed on the APTT test (activated partial thromboplastin time) and the parameters of thromboelastogram (TEG).

Results
It was found that the intranasal administration of Selank to rats showed the presence of anticoagulant and antiplatelet activity in blood plasma under conditions of endothelial dysfunction according to APTTV and TEG parameters. So Selank increased the APTT by 30% compared with that in rats with dysfunction of the endothelium, Selank + L-name returned this parameter to the control level. After the subsequent withdrawal of the drug against the background of L-name, a similar pattern was observed: Selank increased the APTT by 20%.

Conclusion
So, arginine-containing glyprolin Selank showed anticoagulant and antiplatelet activity, and in the presence of Selank there was no endothelial dysfunction caused by L-name. Under conditions of cancellation of the oligopeptide, but continuing dysfunction, its trace positive effects on the parameters of the hemostatic system were noted.

Session topic: 35. Thrombosis and vascular biology & translational Research

Keyword(s): Anticoagulation, Anti-platelet therapies, Antithrombotic, Endothelial dysfunction

Abstract: PB2522

Type: Publication Only

Background
Peptides of a glyproline series, including tripeptides PRO-GLY-PRO (PGP), are formed in the body during the hydrolysis of collagen and elastin. They carry out peptidergic regulation in the body. Multiple studies have shown that glyiprolines are effective and have antiplatelet and anticoagulant properties. Recent experimental data indicate an increase in the effects of glyiprolines when different amino acids are added to the protein structure. Thus, the amino acid arginine ARG (R) increases antithrombotic effects in the body due to the release into the bloodstream of NO.

Aims
Study an influence of arginine-containing peptide Selank on the parameters of the hemostasis system against the background of endothelial dysfunction.

Methods
Endothelial dysfunction was caused by repeated administration of a solution of NO-synthase inhibitor - L-name at a concentration of 10 mg/kg. As the drug, Selank peptide THR-LYS-PRO-ARG-PRO-GLY-PRO (TKPRPGP) was intranasal used at a concentration of 100 μg/kg. All animal experiments were conducted in accordance with ethical principles and documents of the European Convention for the Protection of Vertebrates. White Wistar rats (300 g) were divided into 4 groups: 3 test groups (rats receiving Selank; L-name; Selank + L-name); 1 group - control (NaCl). The substances were administered for 7 days daily every 24 hours. On the 8th day, blood was taken from the jugular vein and a series of experiments was conducted to determine the effect of drugs on the parameters of hemostasis. After the cancellation of Selank, but the continued introduction of L-name, after 7 days, a series of experiments were repeated. The studies were performed on the APTT test (activated partial thromboplastin time) and the parameters of thromboelastogram (TEG).

Results
It was found that the intranasal administration of Selank to rats showed the presence of anticoagulant and antiplatelet activity in blood plasma under conditions of endothelial dysfunction according to APTTV and TEG parameters. So Selank increased the APTT by 30% compared with that in rats with dysfunction of the endothelium, Selank + L-name returned this parameter to the control level. After the subsequent withdrawal of the drug against the background of L-name, a similar pattern was observed: Selank increased the APTT by 20%.

Conclusion
So, arginine-containing glyprolin Selank showed anticoagulant and antiplatelet activity, and in the presence of Selank there was no endothelial dysfunction caused by L-name. Under conditions of cancellation of the oligopeptide, but continuing dysfunction, its trace positive effects on the parameters of the hemostatic system were noted.

Session topic: 35. Thrombosis and vascular biology & translational Research

Keyword(s): Anticoagulation, Anti-platelet therapies, Antithrombotic, Endothelial dysfunction

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