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The Effects of KKRRPGP (Lys-Lys-Arg-Arg-Pro-Gly-Pro) and KRRKPGP (Lys-Arg-Arg-Lys-Pro-Gly-Pro) Peptides on Hemostasis Parameters, Lipid Profile, Blood Glucose Level, and Body Weight Changes in Rats with Metabolic Syndrome and Endothelial Dysfunction

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Abstract—

Intranasal administration of lysine- and arginine-containing peptides Lys-Lys-Arg-Arg-Pro-Gly-Pro and Lys-Arg-Arg-Lys-Pro-Gly-Pro was performed daily at a single dose of 100 µg/kg for 7 days on laboratory rats with experimental metabolic syndrome and endothelial dysfunction. Metabolic syndrome was modeled by a high-calorie diet maintained throughout the experimental period, while endothelial dysfunction was simulated by daily intraperitoneal injection of L–NAME at a single dose of 10 mg/kg for 5 days. It was found that these peptides had anticlotting, hypoglycemic, and lipid-lowering effects and reduced body weight gain in experimental rats. They affected both primary (vascular-platelet) hemostasis, decreasing platelet aggregation, and all elements of plasma hemostasis by increasing anticoagulant, fibrin-depolymerizing, and enzymatic fibrinolytic activities as well as anti-fibrin-stabilizing properties of plasma and reducing the concentration of fibrinogen in it. At the same time, the studied peptides diminished the content of total cholesterol, low-density lipoprotein cholesterol, and triglycerides, while increasing the concentration of high-density lipoprotein cholesterol. These effects were observed 20 h after the last administration of peptides and persisted, although to a lesser extent, 7 days (168 h) after treatment withdrawal. In this regard, the prolonged action can be considered for both glyproline peptides containing lysine and arginine aminoacid residues in their structure and their ability to protect the body from the development of metabolic diseases and endothelial dysfunction. The maximum effects were provided by the Lys-Arg-Arg-Lys-Pro-Gly-Pro peptide, which may be associated with its structural features.

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Funding

The study was conducted within the “Physiological Regulators of Coagulative and Anticoagulative Systems in Normal and Pathological Conditions” State Task no. АААА–А16–16021660094–0 at the premises of the Institute of Molecular Genetics of Kurchatov National Research Center.

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Authors and Affiliations

  1. Institute of Molecular Genetics, Kurchatov Institute, Russian Academy of Sciences, 123182, Moscow, Russia

    N. F. Myasoedov & L. A. Andreeva

  2. Kudryashov Laboratory of Blood Protection Systems, Department of Biology, Moscow State University, 119234, Moscow, Russia

    L. A. Lyapina, T. Yu. Obergan, M. E. Grigorjeva & T. A. Shubina

Authors
  1. N. F. Myasoedov
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  2. L. A. Lyapina
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  3. T. Yu. Obergan
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  4. M. E. Grigorjeva
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  5. T. A. Shubina
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  6. L. A. Andreeva
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Corresponding authors

Correspondence to T. Yu. Obergan, M. E. Grigorjeva, T. A. Shubina or L. A. Andreeva.

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Conflict of interests. The authors declare that they have no conflicts of interests.

Statement on the welfare of animals. All experiments were conducted in accordance with the ethical principles of using laboratory animals and approved by the local ethical committee (Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia).

ADDITIONAL INFORMATION

Lyapina ORCID 0000-0002-8983-652X

Obergan ORCID 0000-0002-3760-3943

Grigorjeva ORCID 0000-0003-0469-3943

Shubina ORCID 0000-0003-1092-8382

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Translated by E. Sherstyuk

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Myasoedov, N.F., Lyapina, L.A., Obergan, T.Y. et al. The Effects of KKRRPGP (Lys-Lys-Arg-Arg-Pro-Gly-Pro) and KRRKPGP (Lys-Arg-Arg-Lys-Pro-Gly-Pro) Peptides on Hemostasis Parameters, Lipid Profile, Blood Glucose Level, and Body Weight Changes in Rats with Metabolic Syndrome and Endothelial Dysfunction. Moscow Univ. Biol.Sci. Bull. 76, 7–13 (2021). https://doi.org/10.3103/S009639252101003X

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  • DOI: https://doi.org/10.3103/S009639252101003X

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