Correction of functional disorders in ADMA-like preeclampsia with derivatives of the peptide imitating erythropoietin α-helix B
https://doi.org/10.21626/vestnik/2020-2/06
Abstract
Objective. The aim of the study is to investigate the correction of functional disorders in ADMA-like preeclampsia with derivatives of the peptide imitating erythropoietin α-helix B.
Materials and methods. The study was performed in 120 white female Wistar rats weighing 250-300 g. ADMA-like preeclampsia was used as experimental preeclampsia. To assess the effectiveness of the pharmacological agents used, blood pressure, microcirculation in the placenta, and proteinuria were recorded, the content of final NO metabolites in the blood plasma was determined, and the coefficient of endothelial dysfunction was calculated. 50 μg / kg polypeptides (P-αB3 and P-αB4) were used as pharmacological agents, obtained by attaching to the original 11-amino acid peptide PHBSP [PubChem CID: 91810664], which is the amino acid chain Pyr-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser (QEQLERALNSS) of KGD group from different ends of the chain.
Results. The use of the studied derivatives of peptide imitating erythropoietin α-helix B with ADMA-like preeclampsia leads to a pronounced correction of disorders. The greatest effect was observed with the introduction of the peptide with the laboratory code P-αB4. A significant decrease in systolic and diastolic pressure was noted, respectively, improved microcirculation in the placenta, restoration of the NO-synthesizing function of the endothelium, and a decrease in proteinuria.
Conclusion. The results obtained indicate the prospect of further research on the effectiveness of short-chain derivatives of erythropoietin imitating its α-helix B for the correction of functional disorders in preeclampsia.
About the Authors
Vladimir V. GureevRussian Federation
DM, Professor of Department of Pharmacology and Clinical Pharmacology
Mikhail V. Korokin
Russian Federation
DM, Associate Professor, Professor of Department of Pharmacology and Clinical Pharmacology
Ivan V. Golubev
Russian Federation
PhD-applicant of Department of Pharmacology and Clinical Pharmacology
Mikhail V. Pokrovsky
Russian Federation
DM, Professor of Department of Pharmacology and Clinical Pharmacology, Head of Research Institute of Pharmacology of Living Systems
Adelaida V. Polyanskaya
Russian Federation
PhD-applicant of Department of Pharmacology and Clinical Pharmacology
Dmitriy B. Kuzmin
Russian Federation
PhD-applicant of Department of Pharmacology and Clinical Pharmacology
References
1. Anciferova O.E., Lokteva T.I., Severinova O.V., Jurakova A.V., Kuznecov S.L., Gureev V.V., Zatolokina M.A., Zatolokina E.S. Results of the morphological research of structural organization of the rat placenta at the late pregnancy. Journal of Volgograd State Medical University.2019;4(72):33-36 (in Russ.). DOI: 10.19163/1994-9480-2019-4(72)-33-36
2. Korokin M.V., Soldatov V.O., Tietze A.A., Golubev M.V., Belykh A.E., Kubekina M.V., Puchenkova O.A., Denisyuk T.A., et al. 11-amino acid peptide imitating the structure of erythropoietin α-helix b improves endothelial function, but stimulates thrombosis in rats. Pharmacy & Pharmacology. 2019;7(6):312-320. DOI: 10.19163/2307-9266-2019-7-6-312-320
3. Severinova O.V., Lazareva G.A., Zhilinkova L.A., Gureeva A.V. Pharmacological effects of the combined administration of a small dose of Acetylsalicylic acid and methyldopa in ADMA-like preeclampsia. Research Results in Biomedicine. 2020;6(1):94-106 (in Russ.). DOI: 10.18413/2658-6533-2020-6-1-0-8
4. Skachilova S.Ya., Kotelnikova A.S., Timokhina A.S., Shcheblykina O.V. Evaluation of antihypoxic activity of ethylmethylhydroxipyridine sukcinate in in vitro experiments. Research Results in Biomedicine. 2018;4(3):70-75 (in Russ.). DOI: 10.18413/2313-8955-2018-4-3-0-7
5. Chahirova A.A., Kovtun E.V., Ogay M.A., Stepanova E.F., Nam N.L. Development of the composition and analysis of suppositories of antihemorrhoidal action. Research Results in Biomedicine. 2018;4(4):52-59 (in Russ.). DOI: 10.18413/2313-8955-2018-4-4-0-6
6. Jurakova A.V., Lokteva T.I., Kuznecov S.L., Zatolokina M.A., Zatolokina E.S., Gureev V.V. Studying the efficiency of erythropoeetin derivatives during correction of disturbances during recreampsion in experiment. Journal of Volgograd State Medical University. 2019;3(71):78-82 (in Russ.). DOI: 10.19163/1994-9480-2019-3(71)-78-82
7. Yurakova A.V., Skachilova S.Ya., Danilenko L.M., Zatolokina M.A., Zatolokina E.S., Gureeva A.V. Study of efficiency of 3-oxypiridine derivatives in correction of disorders in the conditions of experimental preeclampsia. Journal of Volgograd State Medical University. 2020;1(73):133-136 (in Russ.). DOI: 10.19163/1994-9480-2020-1(73)-133-136
8. Ducray J.F., Naicker T., Moodley J. Pilot study of comparative placental morphometry in preeclamptic and normotensive pregnancies suggests possible maladaptations of the fetal component of the placenta. Eur J Obstet Gynecol Reprod Biol. 201;156(1):29-34. DOI: 10.1016/j.ejogrb.2010.12.038
9. Fang M.R., Li J.C. Evaluation of the efficacy of ligustrazine collaborated with magnesium sulfate in the treatment of pregnancy-induced hypertension in rats. Shi Yan Sheng Wu Xue Bao. 2005;38(1):45-53 (in Chin.)
10. Gureev V.V., Pokrovskii M.V., Korokin M.V., Gudyrev O.S., Philippova O.V., Dolzhikov A.A., Lazareva G.A. Correction of ADMA-induced preeclampsia with use of tetrahydrobiopterin and selective inhibitor of arginase II ZB49-0010. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 2015;6(5):1538-1541. DOI: 10.18413/2313-8955-2015-1-4-66-68
11. Khadieva T.A., Pokrovskaya T.G., Belousova Y.V. Pharmacological correction of endothelial dysfunction using ademethionin and taurine. Research Results in Pharmacology. 2019;5(2):13-21. DOI: 10.3897/rrpharmacology.5.32730
12. Minoux H., Chipot C., Brown D., Maigret B. Structural analysis of the KGD sequence loop of barbourin, an αIIbβ3-specific disintegrin. J Comput Aided Mol Des. 2000;14(4):317-327. DOI: 10.1023/a:1008182011731
13. Pankiewicz K., Szczerba E., Maciejewski T., Fijałkowska A. Non-obstetric complications in preeclampsia. Prz Menopauzalny. 2019;18(2):99-109. DOI: 10.5114/pm.2019.85785
14. Peresypkina A.A., Dovgan A.P., Belousova Y.V. Imidazoline receptors agonists: possible mechanisms of endothelioprotection. Research Results in Pharmacology. 2018;4(2):11-18. DOI: 10.3897/rrpharmacology.4.27221
15. Pokrovskaya T.G., Korokin M.V., Gudyrev O.S., Sernov L.N., Osipova O.A., Chadieva T.A., Dovgan A.P. Combined pharmacological correction of the metabolic pathways of L-arginine/nohy-poestrogenemia in the simulation of deficiency of nitric oxide. International Journal of Pharmacy and Technology. 2016;8(3):15175-15181
16. Ruiqiong M.A., Sun M., Yang Z. Effects of preeclampsia-like symptoms at early gestational stage on feto-placental outcomes in a mouse model. Chin Med J (Engl). 2010;123(6):707-712
17. Shaheen G., Jahan S., Ain Q.U., Ullah A., Afsar T., Almajwal A., Alam I., Razak S. Placental endothelial nitric oxide synthase expression and role of oxidative stress in susceptibility to preeclampsia in Pakistani women. Mol Genet Genomic Med. 2019;8(1):e1019. DOI: 10.1002/mgg3.1019
18. Sheppard S.J., Khalil R.A. Risk Factors and Mediators of the Vascular Dysfunction Associated with Hypertension in Pregnancy. Cardiovasc Hematol Disord Drug Targets. 2010;10(1);33-52. DOI: 10.2174/187152910790780096
19. Soldatov V.O., Shmykova E.A., Pershina M.A., Ksenofontov A.O., Zamitsky Y.M., Kulikov A.L., Peresypkina A.A., Dovgan A.P., et al. Imidazoline receptors agonists: possible mechanisms of endothelioprotection. Research Results in Pharmacology. 2018;4(2):11-18. DOI: 10.3897/rrpharmacology.4.27221
20. Stupakova E.G., Lazareva G.A., Gureev V.V., Dolzhikova I.N., Zhilinkova L.A., Gureeva A.V. L-NAME-induced Preeclampsia: correction of functional disorders of the hemostasis system with Resveratrol and Nicorandil. Research Results in Pharmacology. 2019;5(2):1-12. DOI: 10.3897/rrpharmacology.5.35316
21. Un Nisa S., Shaikh A.A., Kumar R. Maternal and Fetal Outcomes of Pregnancy-related Hypertensive Disorders in a Tertiary Care Hospital in Sukkur, Pakistan. Cureus. 2019;11(8):e5507. DOI: 10.7759/cureus.5507
Review
For citations:
Gureev V.V., Korokin M.V., Golubev I.V., Pokrovsky M.V., Polyanskaya A.V., Kuzmin D.B. Correction of functional disorders in ADMA-like preeclampsia with derivatives of the peptide imitating erythropoietin α-helix B. Kursk Scientific and Practical Bulletin "Man and His Health". 2020;(2):42-49. (In Russ.) https://doi.org/10.21626/vestnik/2020-2/06