Correction of rats’ systemic and cerebral blood circulation with the cerebral ischemia-reperfusion model using new neuropeptides, ACTH15-18 derivatives

Authors

  • R. D. Deiko National University of Pharmacy, Ukraine
  • S. Yu. Shtrygol National University of Pharmacy, Ukraine
  • O. O. Kolobov "Research Institute of Pure Biochemicals", Russian Federation
  • O. A. Khodakivskiy National Pirogov Memorial Medical University, Ukraine
  • L. B. Ivantsyk National University of Pharmacy, Ukraine

DOI:

https://doi.org/10.24959/cphj.15.1348

Keywords:

experiment, cerebral blood circulation, systemic blood circulation, ischemia-reperfusion, neuropeptides

Abstract

Cerebrovascular diseases are leading problems of the modern medicine and pharmacy. That is why creation of new neuroprotectors and their introduction into clinical practice is a topical issue. A series of oligopeptides, 15-18 adrenocorticotropic hormone link derivatives has been created. These neuropeptides are compounds with the general formula of Acetyl-Lys-Lys-Arg-Arg-amide. They are nontoxic compounds and resistant to action of blood aminopeptidases. Their composition includes unnatural D-aminoacids and their N-methylated forms. The previous studies have determined their anti-ischemic and nootropic action, and a favourable spectrum of psychotropic properties. The question about mechanisms of the anti-hypoxic action of compound Acetyl-(D-Lys)-Lys-Arg-Arg-amide (KK-1) remains open. The aim of our investigation is to study effect of neuropeptide KK-1 on the hemodynamic parameters, as well as blood oxygenation against the background of ischemia-reperfusion in the rats’ brain. The volume speed of the blood flow in the internal carotid artery, blood pressure in the femoral artery, the central venous pressure and blood oxygenation were measured. The ability of peptide KK-1 to restore the initial level of blood pressure in the femoral artery and central venous pressure within 7 days has been found. The volume speed of the blood flow in the internal carotid artery was sufficient for brain blood supply during all post-ischemic period. The level of blood oxygenation varied from 97% to 98%, tending to the norm. By the effect on the indicators listed neuropeptide KK-1 exceeds the action of the reference drug citicoline. The positive effect of peptide KK-1 on the performance of the system and cerebral blood flow and blood oxygen saturation against the background of cerebral ischemia confirms its anti-ischemic and cerebroprotective effect. The pharmacological drug is promising for further experimental and clinical studies.

References

Дейко Р.Д. Экспериментальное исследование церебропротекторных и антиамнестических свойств новых нейроактивных пептидов / Р.Д. Дейко, С.Ю. Штрыголь, А.А. Колобов // Об-зоры по клинической фармакологии и лекарственной терапии. – 2013. – Т.11. – С.46.

Зозуля І.С. Епідеміологія цереброваскулярних захворювань в Україні [Текст] / І.С. Зозуля, А.І. Зозуля // Український медичний часопис. – 2011. – № 5 (85). – С. 38 – 41.

Ковалицкая Ю. А. Стресс-протекторная активность синтетического пептида CH3CO-Lys-Lys-Arg-Arg-NH2 (протектина) / Ю. А. Ковалицкая, В. Б. Садовников, Ю. А. Золотарев, Е. В. Наволоцкая // Биоорг. химия. – 2009. - №35 (4). – С. 493 – 500 c.

Патент № 2537560 С2 Россия, МПК С07К 5/11 (2006.1) А61К 38/07 (2006.1) А61Р 25/00 (2006.1) Тетрапептид и средство, обладающее церебропротекторной и антиамнестической активностями (варианты) / Дейко Р.Д., Кампе-Немм Е.А., Колобов А.А., Шпень В.М., Штрыголь С.Ю.; заявитель и патентообладатель Общество с ограниченной активностью «Научно-производственная фирма «ВЕРТА» (RU). – Заявка 2013119051/04, 25.04.2013; заявл. 25.04.2013; опубл. 10.01.2015. – Бюл. №1, 2015. – 13 с.

Ходаківський О. А. Експериментальне дослідження впливу адемолу (сполуки ЮК-1) на коронарну та системну гемодинаміку в умовах наркозу / О. А. Ходаківський // Biomedical and biosocial anthropology. – 2011. – № 16. – С. 7-9.

Ходаковский А. А. Особенности формирования постреперфузионного повреждения нейронов – характеристика модели «ишемия-реперфузия». Новые направления и перспективы развития современной церебропротекторной терапии ишемического инсульта / А. А. Ходаковский, Л. И. Маринич, О. В. Багаури // Врач-аспирант. – 2013. - № 3 (58). – С. 69-76.

Шведський В. В. Експериментальне порушення мозкового кровообігу на тлі алоксанового цукрового діабету: характеристика моделі / В. В. Шведський, О. А. Ходаківський // Буковинський медичний вісник. – 2012. – Т.16, №1 (61). – С. 150-156.

Encyclopedia of Molecular Pharmacology [Text] / Edited by Offermans S., Rosenthal W. – 2nd edition. – Berlin, Heidelberg, New York: Springer-Verlag, 2008. – 1505 p. Manual of Stroke Models in Rats [Text] / Edited by Yanling Wang-Fisher. – London, New York: CRC Press, 2009. – 332 p.

Molecular pharmacology: from DNA to drug discovery [Text] / Dickenson J. [et al.] – New York: John Wiley&Sons Ltd., 2013. – 409 p.

New Strategies in Stroke Intervention: Ionic Transporters, Pumps and New Channels [Text] / Edited by Annunziato L. – New York: Humana Press, 2009. – 254 p.

Nouh A. Ischemic posterior circulation stroke: a review of anatomy, clinical presentations, diagnosis, and current management / A. Nouh [et al.] // Frontiers in Neurology. – 2014. – Vol. 5. - Article 30. Stroke – Pathophysiology, Diagnosis, and Management [Text] / Mohr J.P. – Saunders, 2011. – 1520 p.

Downloads

Published

2015-12-01

Issue

Vol. 19 No. 4 (2015)

Section

Pre-clinical studies of new drugs

License

Copyright (c) 2015 National University of Pharmacy

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish with this journal agree to the following terms:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).