CORRECTION OF MANIFESTATIONS OF THE EXPERIMENTAL METABOLIC SYNDROME IN RATS WITH SOME ARGININE-CONTAINING PEPTIDES
Abstract
An important task of biomedical research is the functional characterization of new regulatory glyproline peptides, which are able to provide regulatory effect on the functional state of the haemostatic system, lipid and carbohydrate metabolism in the organism. In the present study used a model of experimental metabolic syndrome that involves continuous feeding rats of high calorie food. This leads to increased clotting, glucose concentration, levels of total cholesterol, LDL cholesterol, triglycerides in the blood and to the development of obesity. 6 weeks after development of metabolic syndrome arginine-containing peptides (Arg-Glu-Arg-Pro-Gly-Pro, Arg-Glu-Arg-Val-Gly-Pro, Arg-Glu-Arg-Gly-Pro) were administrated to rats intranasal way once daily for 7 days. It was found that these peptides have the unique combined effects on organism, because they normalized the parameters of lipid metabolism, haemostatic system and the concentration of glucose in the blood. This corrective effect of the peptides was detected 20 h after the last drug administration and persisted for 168 h even in the continued maintenance of rats on a high-calorie diet. The investigated glyproline can be attributed to the therapeutic normoglycemic and lipid-lowering drugs. They block the accumulation of new fat deposits in the body and also have anticoagulant and antithrombotic effects in case of the disturbances of carbohydrate and fat metabolism. The most pronounced and stable positive effects on the organism it was established for peptide Arg-Glu-Arg-Pro-Gly-Pro.
About the Authors
L. A. Lyapina
Lomonosov Moscow State University
Russian Federation
Russian Federation
Laboratory of defense systems of the blood, Department of human and animal physiology, School of Biology
Leninskiye Gory 1/12, Moscow, 119234, Russia
M. E. Grigorjeva
Lomonosov Moscow State University
Russian Federation
Russian Federation
Laboratory of defense systems of the blood, Department of human and animal physiology, School of Biology
Leninskiye Gory 1/12, Moscow, 119234, Russia
T. Y. Obergan
Lomonosov Moscow State University
Russian Federation
Russian Federation
Laboratory of defense systems of the blood, Department of human and animal physiology, School of Biology
Leninskiye Gory 1/12, Moscow, 119234, Russia
N. F. Myasoedov
Institute of molecular genetics. Russian Academy of Sciences
Russian Federation
Russian Federation
Kurchatov sq. 2, Moscow, 123182, Russia
L. A. Andreeva
Institute of molecular genetics. Russian Academy of Sciences
Russian Federation
Kurchatov sq. 2, Moscow, 123182, Russia
Russian Federation
Kurchatov sq. 2, Moscow, 123182, Russia
References
1. Shubina T.A., Grigorjeva M.E., Lyapina L.A., Obergan T.Y., Myasoedov N.F., Andreeva L.A. Hypoglycemic and anticoagulant effects of tetrapeptide Pro-Gly-Pro-Leu in hypercholesterolemia // Bull. Exp. Biol. Med. 2014. Vol. 158. N 1. P. 30–33.
2. Lyapina L.A., Grigorieva M.E., Obergan T.Yu, Shubina T.A., Andreeva L.A., Myasoedov N.F. Peptide regulation of metabolic processes under hypercholesterolemia conditions of an organism // Biol. Bull. 2015. Vol. 42. N 6. P. 546–555.
3. Andreeva L.A., Myasoedov N.F., Lyapina L.A., Grigor’eva M.E., Obergan T.Y., Shubina T.A. Effect of the PRO-GLY-PRO peptide on hemostasis and lipid metabolism in rats with hypercholesterolemia // Dokl. Biol. Sci. 2013. Vol. 453. N 1. P. 333–335.
4. Ferrell J.E., Martin G.S. Tyrosine-specific protein phosphorylation is regulated by glycoprotein IIb-IIIa in platelets // Proc. Natl. Acad. Sci. U.S.A. 1989. Vol. 86. N 7. P. 2234–2238.
5. Gorbachisky I., Akpinar H., Assimos D.G. Metabolic syndrome and urological diseases // Rev. Urol. 2010. Vol. 12. N 4. P. 157–180.
6. Xiao C., Hsieh J., Adeli K., Lewis G.F. Gut-liver interaction in triglyceride-rich lipoprotein metabolism // Am. J. Physiol. Endocrinol. Metab. 2011. Vol. 301. N 3. Р. E429–E446.
7. Баркаган З.С., Костюченко Г.И. Метаболически-воспалительная концепция атеротромбоза и новые подходы к терапии больных // Бюл. СО РАМН. 2006. № 2 (120). С. 132–138.
8. Watson T., Arya A., Sulke N., Lip G.Y.H. Relationship of indices of inflammation and thrombogenesis to arithmia burden in paroxysmal arterial fibrillation // Chest. 2010. Vol. 137. N 4. P. 869–876.
9. Kong X., Zhang D.Y., Wu H.B., Li F.X. Losartan and pioglitazone ameliorate nephropathy in experimental metabolic syndrome rats // Biol. Pharm. Bull. 2011. Vol. 34. N 5. P. 693–698.
10. Vila L., Rebollo A., Adalsteisson G.S., Alegre T.M., Merlos M., Roglans N., Laguna J.C. Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats at atrovastatin treatment // Toxicol. Appl. Pharmacol. 2011. Vol. 251. N 1. P. 32–40.
11. Малинин В.В. Средство для коррекции метаболического синдрома // Патент России № 2458935. 2012. Бюл. № 23.
12. Коркушко О.В., Чижова В.П., Шатило В.Б., Хавинсон В.Х. Эффективность тетрапептида Панкраген форме у пожилых людей с преддиабетическими нарушениями углеводного обмена // Усп. геронтол. 2013 Т. 26. № 2. С. 297–308.
13. Жернакова Ю.В., Мычка В.Б., Чазова И.Е. Место комбинированной терапии в лечении больных с метаболическим синдромом // Кардиоваск. тер. проф. 2010. T. 9. № 4. С. 1–4.
14. Stief T.W. Inhibition of thrombin in plasma by heparin or arginine // Clin. Appl. Thromb. Hemost. 2007. Vol. 13. N 2. P. 146–153.
15. Vasilijević A., Buzadžić B., Korać A., Petrović V., Janković A., Korać B. Benefical effects of L- arginine-nitric oxide – producing pathway in rats treated with alloxan // J. Physiol. 2007. Vol. 584. N 3. P. 921–933.
16. Myasoedov N.F., Lyapina L.A., Grigorjeva M.E., Obergan T.Y., Shubina T.A., Andreeva L.A. Мechanism for glyproline protection in hypercholesterolemia // Pathophysiol. 2016. Vol. 23. N 1. P. 27–33.
17. Ляпина Л.А., Григорьева М.Е., Оберган Т.Ю., Шубина Т.А. Теоретические и практические вопросы изучения функционального состояния противосвертывающей системы крови. М.: Адвансед Солюшнз, 2012. 160 с.
18. Ikee R., Hamasaki Y., Oka M., Maesato K., Mano T., Moriya H., Ohtake T., Kobayashi S. Clinical: high-density lipoprotein cholesterol and left ventricular mass index in peritoneal dialysis // Perit. Dial. Int. 2008. Vol. 28. N 2. P. 611–616.
19. Кузник Б.И., Хавинсон В.Х., Тарновская С.И., Линькова Н.С. Эпигенетическое действие регуляторных пептидов на цитокиновый профиль и систему гемостаза // Вестн. гематол. 2013. Т. 9. № 2. С. 29–33.
20. Glaudemans A.W., Slart R.H., Bozzao A., Bonanno E. Molecular imaging in atherosclerosis // Eur. J. Nucl. Med. Mol. Imaging. 2010. Vol. 37. N 12. Р. 2381–2397.
21. Meade L.T. Practical use of exenatide and pramlintide for the treatment of type 2 diabetes // J. Pharm. Pract. 2009. Vol. 22. N 6. P. 540–545.
22. Shabalina A.A., Lyapina L.A., Rochev D.L., Kostyreva M.V., Tanashyan M., Suslina T.A. In vitro lipid lowering and fibrinolytic effects of regulatory leucine containing glyprolines in human blood // Biol. Bull. 2015. Vol. 42. N 1. P. 74–77.
23. Hasan A.A., Wernock M., Nieman M., Srikanth S., Mahdi F., Krishnan R., Tulinsky A., Schmaier A. Mechanisms of Arg-Pro-Gly-Phe inhibition of thrombin // J. Physiol. Heart Circ. Physiol. 2003. Vol. 285. N 1. P. 183–193.
Review
For citations:
Lyapina L.A., Grigorjeva M.E., Obergan T.Y., Myasoedov N.F., Andreeva L.A. CORRECTION OF MANIFESTATIONS OF THE EXPERIMENTAL METABOLIC SYNDROME IN RATS WITH SOME ARGININE-CONTAINING PEPTIDES. Vestnik Moskovskogo universiteta. Seriya 16. Biologiya. 2017;72(2):92-98. (In Russ.)
Views:
286
Email this article 