Influence of a new derivative of 4-aminobutanoic acid on the level of neuromediatory aminoacids, neuromediators and the state of the rats’ hypocamp in conditions of brain ischemia

Authors

DOI:

https://doi.org/10.15587/2519-4852.2021.230305

Keywords:

new derivative of 4-aminobutanoic acid, brain ischemia, neuroprotective effect, hippocampus, Picamilon

Abstract

The aim: to investigate the effect of a new derivative of 4-aminobutanoic acid (compounds KGM-5) on the level of neurotransmitters and neurotransmitter amino acids and the structural-functional state of the hippocampus of rats with acute cerebrovascular accident (ACVA).

Materials and methods. ACVA was reproduced in rats by occlusion of the left carotid artery under anesthesia (sodium thiopental (35 mg/kg) intraperitoneally (i/p). 5 groups of animals were used: intact control (IC, n=6), untreated animals with ACVA (CP, n=13); animals with ACVA (n=14), which were treated for 5 days with KGM-5 at a dose of 30 mg/kg i/p, animals with ACVA (n=13), who received i/p comparison drug “Picamilon” (17 mg/kg). There was a group of pseudo-operated animals (POA, n=8). Withdrawal of animals from the experiment was performed on day 6 after modeling ACVA by painless euthanasia under anesthesia. Histological examinations of CA1 and CA3 zones of the ventral hippocampus were performed with staining of sections with thionine by the method of Nissl and hematoxylin, eosin. In the rat brain, neurotransmitter amino acids and neurotransmitters were identified. Statistical processing was performed using the W-Shapiro-Wills test to verify the normality of the distribution and the nonparametric Mann-Whitney U-test. The accepted significance level is p<0.05.

Results. Under the influence of the compound KGM-5 and “Picamilon” in the CA1 zone of the hippocampus, the number of normochromic neurons increased by 20 % and 16.6 %, respectively, hyperchromic pycnomorphic neurons and shadow cells decreased respectively by 5.8; 2.9 times and 6.3; 3.5 times, the index of alteration of neurons decreased by 6 times and 4.8 times, respectively, the area of ​​the perikaryon of these neurons increased by 39.7 % and 77.8 %, respectively, compared with KP (p<0.05). Both studied agents showed a less pronounced normalizing effect on the CA3 area of the hippocampus. The new compound KGM-5 showed a normalizing effect similar to “Picamilon” on the level of neurotransmitter amino acids and neurotransmitters in the brain of rats with ACVA.

Conclusions. Therapeutic administration of KGM-5 increases the survival of ventral hippocampal neurons, reducing the relative proportion of irreversibly altered cells, and helps to restore impaired levels of neurotransmitter amino acids and neurotransmitters in the brain of rats with ACVA.

The neuroprotective effect of the new compound KGM-5 corresponds to this comparison drug “Picamilon”

Author Biographies

Oksana Mishchenko, National University of Pharmacy

Doctor of Pharmaceutical Sciences, Professor

Department of Clinical Pharmacology

Institute of Advanced Training of Pharmacy Specialists

Natalia Palagina, National University of Pharmacy

Postgraduate Student

Department of Clinical Pharmacology

Institute of Advanced Training of Pharmacy Specialists

Yuliia Larianovskaya, National University of Pharmacy

PhD, Senior Researcher

Educational and Scientific Institute of Applied Pharmacy

Tatyana Gorbach, Kharkiv National Medical University

PhD, Associate Professor

Department of Biological Chemistry

Viktor Khomenko, Donetsk National Medical University

Doctor of Pharmaceutical Sciences, Professor

Department of Pharmacy and Pharmacology

Nataliia Yasna, T. H. Shevchenko National University "Chernihiv Colehium"

PhD, Associate Professor

Department of Chemistry, Technology and Pharmacy

References

  1. Mischenko, T. S. (2017). Cognitive violations in the practice of family doctor (theurgency of the problem, risk factors, pathogenesis,treatment options and preventions). Family Medicine, 1 (69), 21–25. doi: http://doi.org/10.30841/2307-5112.1(69).2017.102983
  2. Kovalchuk, V. V. (2020). Cognitive Dysfunction. A Modern View on Etiology, Pathogenesis, Diagnostics and Therapy. Effektivnaia farmakoterapіia, 16 (31), 40–52.
  3. Lokshina, A. B. (2020). Modern aspects of diagnosis and treatment of mild cognitive impairment. Russian Journal of Geriatric Medicine, 3, 199–204. doi: http://doi.org/10.37586/2686-8636-3-2020-199-204
  4. Sahathevan, R., Brodtmann, A., Donnan, G. A. (2011). Dementia, Stroke, and Vascular Risk Factors; a Review. International Journal of Stroke, 7 (1), 61–73. doi: http://doi.org/10.1111/j.1747-4949.2011.00731.x
  5. Levin, O. S. (2014). Diagnostika i lechenie dementsii v klinicheskoi praktike. Moscow: MEDpressinform, 256.
  6. Kovalchuk, V. V., Barantsevych, E. R. (2017). Chronic Cerebral Ischemia. Current Understanding of Etiopathogenesis, Diagnostics and Therapy. Effektivnaia farmakoterapіia, 19, 26–32.
  7. Mishchenko, O. Ya., Holik, M. Yu., Hrytsenko, I. S., Komisarenko, A. M., Palahina, N. Yu., Mishchenko, M. V. (2017). Pat. No. 120512 UA. Zastosuvannia pokhidnykh 4- aminobutanovoi kysloty yak nootropnykh zasobiv. MPK: (206), A 61K 31/197, A61P 25/00. No. u201703627; declareted: 13.04.2017; published: 10.11.2017, Bul. No. 21.
  8. Gantsgorn, E. V., Khloponin, D. P., Khloponin, P. A. (2015). Nootropics and melaxen’ neuroprotectional activity morphopharmacological analysis in rats’ acute cerebral ischemia. Medical Herald of the South of Russia, 3, 42–46.
  9. Mironov, A. N.; Mironov, A. N. (Ed.) (2012). Rukovodstvo po provedeniiu doklinicheskikh issledovanii lekarstvennykh sredstv. P. 1. Moscow: Grif i K., 944.
  10. Ulanova, I. P., Sidorov, K. K., Khalepo, A. I. K. (1968). K voprosu ob uchete poverkhnosti tela eksperimentalnykh zhivotnykh pri toksikologicheskom issledovanii. Toksikologiia novykh promyshlennykh khimicheskikh veschestv, 10, 18–25.
  11. Pro zatverdzhennia Poriadku provedennia doklinichnoho vyvchennia likarskykh zasobiv (2009). Nakaz MOZ Ukrainy No. 944. 14.12.2009. Available at: https://zakon.rada.gov.ua/laws/show/z0053-10#Text
  12. European convention for the protection of vertebrate animal used for experimental and other scientific purposes (1986). Stratsburg: Council of Europe, 11.
  13. Merkulov, H. A. (1969). Kurs patolohohystolohycheskoi tekhnyky. Moscow: Medytsyna Lenynhr. otd-nye, 424.
  14. Pyrs, E. (1962). Hystokhymyia: teoretycheskaia y prykladnaia. Moscow, 962 .
  15. Kogan, B. M., Nechaev, N. V. (1979). Chuvstvitelnii i bystrii metod odnovremennogo opredeleniia dofamina, noradrenalina, serotonina i 5-oksiindol-uksusnoi kisloty v odnoi probe. Laboratornoe delo, 5, 301–303.
  16. Zaitseva, T. N., Tiuleneva, I. N. (1958). Metod khromatograficheskogo razdeleniia aminokislot. Laboratornoe delo, 3, 24–30.
  17. Drozdov, N. S., Materanskaia, N. P. (1970). Praktikum po biologicheskoi khimii. Moscow: Vysshaia shkola, 296.
  18. Rebrova, O. Iu. (2006). Statisticheskii analiz meditsinskikh dannykh. Primenenie paketa programm Statistica. Moscow: MediaSfera, 312.
  19. Tverskaia, A. V., Dolzhikov, A. A., Bobyntsev, I. I., Kriukov, A. A., Belykh, A. E. (2014). Morfologicheskie izmeneniia neironov oblastei SA1 I SA3 gippokampa krys pri khronicheskom stresse (morfometricheskoe issledovanie). Chelovek i ego zdorove, 3, 37–41.
  20. El Falougy, H., Kubikova, E., Benuska, J. (2008). The microscopical structure of the hippocampus in the rat. Bratisl. Lek Listy, 109 (3), 106–110.
  21. Gordon R. Ya. (2014). Peculiarities of neurodegeneration in hippocampus fieldsafter kainic acid action in rats. Tsitologiya, 56 (12), 919–925.
  22. Gantsgorn, E. V., Khloponin, D. P., Maklyakov, Yu. S. (2013). Pathophysiological basics of acute brain ischemia modern pharmacotherapy. nootropics and antioxidants’ role in neuroprotection. Medical Herald of the South of Russia, 2, 4–12.
  23. Belenichev, I. F., Bukhtiiarova, N. V., Sereda, D. A. (2010). Sovremennye napravleniia neiroprotektsii v terapii ostrogo perioda patologii golovnogo mozga razlichnogo ґeneza. Mezhdunarodnii nevrologicheskii zhurnal, 2 (32). Available at: http://www.mif-ua.com/archive/article/11994
  24. Chekman, Y. S., Belenychev, Y. F., Demchenko A. V. et. al. (2014). Nootropics in a comlex therapyof chronic cerebral ischemia. Nauka ta innovatsii, 10 (4), 61–75.
  25. Martynova, O. V. (2017). Vliianie farmakologicheskogo prekonditsioni-rovaniia s ispolzovaniem ingibitora FDE-5 tadalafila na ishemicheskie – reperfuzionnye povrezhdeniia golovnogo mozga krys (eksperimentalnoe iscledovanie). Belgorod, 147.

Downloads

Published

2021-04-30

How to Cite

Mishchenko, O., Palagina, N. ., Larianovskaya, Y. . ., Gorbach, T., Khomenko, V. ., & Yasna, N. (2021). Influence of a new derivative of 4-aminobutanoic acid on the level of neuromediatory aminoacids, neuromediators and the state of the rats’ hypocamp in conditions of brain ischemia. ScienceRise: Pharmaceutical Science, (2 (30), 64–71. https://doi.org/10.15587/2519-4852.2021.230305

Issue

Section

Pharmaceutical Science