UDC: 615.031
BBC: Р52.81
Termulaeva R.M., Blinov K.D., Timoshkin D.E., Blinova E.V., Gromova I.A., Shmatok D.O., Pirozhkov A.S., Bunyatyan N.D.
Metabolic profile of the rat brain after reperfusion under experimental treatment with medicinal forms of taurine derivatives
Keywords: brain, reperfusion, occlusion, edema, ischemia, nimodipine, cytokines, taurine
The outcome of reperfusion therapy for acute cerebrovascular accident largely depends on maintaining the viability of penumbral cells. Currently, the role of natural origin compounds as regulators of metabolic processes in the central nervous system is widely studied in the world. The aim of the study was to determine the pharmacological potential of two metal–containing amino acid and ketoacid compounds in the form of a liquid dosage form to correct metabolic disorders in the rat brain caused by cerebral ischemia and subsequent reperfusion. Materials and methods. The study was performed on 72 male sexually mature Wistar rats. Acute cerebral ischemia was reproduced in all animals by intraluminal microfilament injection followed by reperfusion. All the animals were randomly divided into 4 groups, each of which included 18 rats. Animals of the first group (control) received 0.9% sodium chloride solution 10 minutes before modeling acute ischemia and 10 minutes before restoring cerebral blood flow; animals of the second group received a liquid dosage form – 2% solution of LHT–317 (magnesium bis-2-acetaminoethanesulfonate) intravenously at the dose of 12.5 mg/kg; animals of the third group received a liquid dosage form – 2% solution of LHT–318 (zinc salt of 2-aminoethanesulfonic acid) in a single dose of 29 mg/ kg, in the fourth group, rats were given intravenous nimodipine at the dose of 0.8 mg/ kg. After 3, 24, and 48 hours after cerebral perfusion restoration, the rats were excluded from the experiment and the brain was extracted. The level of cerebral edema was determined by measuring the weight of the contralateral hemispheres and subsequent 24-hour tissue drying at the temperature of 110°C, calculating the percentage of fluid in brain tissues, using the Csiba umbelliferone fluorescence pH method, and the tissue concentration of TNF-alpha and interleukin 10 by quantitative ELISA. Statistical analysis of the results was performed using the methods of variational statistics when comparing the means with an error probability of no more than 5%. Research results. In animals of the control group, a day after cerebral perfusion restoration, an increase in edema of brain tissues was noted: by the end of the observation, the proportion of fluid from the total mass of the hemisphere reached 84.3%. In the experimental groups of animals receiving intravenous liquid dosage forms LHT-3-17 and LHT-318 and nimodipine, this indicator was 65.4%, 71.3% and 69.1%, respectively. The restriction of blood supply in the ischemic zone was accompanied by acidification of the environment and the development of tissue acidosis in the control group rats with an average pH value of 6.2. By the end of the first day of observation, both liquid dosage forms of 2-aminoethanesulfonic acid derivatives prevented the development of tissue acidosis by maintaining the pH of the right brain hemisphere at the level of 6.9–7.1. When measuring the tissue concentration of cytokines, the ability of the substances under study to reduce TNF-alpha levels by 35-45% with a compensatory increase in the concentration of interleukin 10 was established. Conclusions. The study proved the activity of liquid dosage forms of new compounds in relation to the prevention of reperfusion brain edema. LHT-317 and LHT-318 in the form of 2% injection solutions reduce TNF-alpha production against the background of metabolic acidosis formation with an increase in pH to 7.1, at this, the effect of LHT-317 began immediately after reperfusion of the medial cerebral artery, whereas the effect of LHT-318 developed 48 hours after cerebral blood flow restoration.
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About authors
- Termulaeva Rita M.
- Candidate of Medical Sciences, Senior Researcher, Pharmacology Laboratory, A.A. Kadyrov Chechen State University, Russia, Grozny (ritaterm@mail.ru; ORCID: https://orcid.org/0000-0001-5300-5700)
- Blinov Kirill D.
- 3rd year Student, N.V. Sclifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenovskiy University), Russia, Moscow (pyrk2@yandex.ru; ORCID: https://orcid.org/0009-0002-7195-2191)
- Timoshkin Dmitry E.
- Researcher, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Russia, Moscow (Dmtimo@mail.ru; ORCID: https://orcid.org/0000-0002-1211-1096)
- Blinova Ekaterina V.
- Doctor of Medical Sciences, Head of the Department of Fundamental Medicine, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute); Professor, Department of Operative Surgery and Topographic Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenovskiy University), Russia, Moscow (bev-sechenov@mail.ru; ORCID: https://orcid.org/0000-0003-0050-0251)
- Gromova Irina A.
- Candidate of Medical Sciences, Department of Pharmacology, National Research Ogarev Mordovia State University, Russia, Saransk (IGromovaa@yandex.ru; ORCID: https://orcid.org/0000-0003-4357-5958)
- Shmatok Danila O.
- Candidate of Medical Sciences, Research Fellow, National Research Nuclear University MEPhI (Moscow Engineering Physics Institute), Russia, Moscow (masonry_25@mail.ru; ORCID: https://orcid.org/0000-0002-9874-3456)
- Pirozhkov Alexander S.
- Post-Graduate Student, Department of Public Health and Healthcare Organization, National Research Ogarev Mordovia State University, Russia, Saransk (pirozhkov1996@yandex.ru; ORCID: https://orcid.org/0000-0003-1895-5342)
- Bunyatyan Natalia D.
- Doctor of Pharmaceutical Sciences, Professor, Expert, Scientific Center on Expertise of Medical Application Products of the Ministry of Health of the Russian Federation, Russia, Moscow (ndbun@mail.ru; ORCID: https://orcid.org/0000-0001-9466-1261)
Article link
Termulaeva R.M., Blinov K.D., Timoshkin D.E., Blinova E.V., Gromova I.A., Shmatok D.O., Pirozhkov A.S., Bunyatyan N.D. Metabolic profile of the rat brain after reperfusion under experimental treatment with medicinal forms of taurine derivatives [Electronic resource] // Acta medica Eurasica. – 2025. – №2. P. 40-47. – URL: https://acta-medica-eurasica.ru/en/single/2025/2/5/. DOI: 10.47026/2413-4864-2025-2-40-47.