Morphological changes in the myocardium of rats with chronic alcohol intoxication after treatment with new GABAand glutamic acid derivatives

Aim. To study pathohistological changes in the myocardium of rats with chronic alcohol intoxication (CAI) after treatment with a new glutamic acid derivative glufimet (compound RSPU-238) and a new gamma-aminobutyric acid (GABA) derivative (compound RSPU-260).Materials and methods. Experiments were p...

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Main Authors: A. A. Nesterova, I. I. Prokofiev, V. N. Perfilova, O. Yu. Evsyukov, M. V. Kustova, I. N. Tyurenkov
Format: Article
Language:English
Published: Siberian State Medical University (Tomsk) 2023-04-01
Series:Бюллетень сибирской медицины
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Online Access:https://bulletin.ssmu.ru/jour/article/view/5136
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author A. A. Nesterova
I. I. Prokofiev
V. N. Perfilova
O. Yu. Evsyukov
M. V. Kustova
I. N. Tyurenkov
author_facet A. A. Nesterova
I. I. Prokofiev
V. N. Perfilova
O. Yu. Evsyukov
M. V. Kustova
I. N. Tyurenkov
author_sort A. A. Nesterova
collection DOAJ
description Aim. To study pathohistological changes in the myocardium of rats with chronic alcohol intoxication (CAI) after treatment with a new glutamic acid derivative glufimet (compound RSPU-238) and a new gamma-aminobutyric acid (GABA) derivative (compound RSPU-260).Materials and methods. Experiments were performed on female Wistar rats aged 10 months. The rats were divided into the following groups: group 1 – intact females; group 2 – a control group which included animals after CAI simulated by replacing drinking water with 10% ethanol solution for 24 weeks; groups 3 and 4 – experimental groups, in which females were intraperitoneally administered with glufimet at a dose of 28.7 mg / kg and RSPU260 at a dose of 25 mg / kg once a day for 14 days after cessation of alcohol solution consumption; group 5 – a group of animals receiving a reference listed drug mildronate at a dose of 50 mg / kg according to a regimen similar to that of the studied compounds. Changes in microstructural and morphometric parameters of the left ventricular myocardium were assessed using light microscopy.Results. In animals after CAI, the cardiomyocyte volume fraction decreased, while the interstitial and vascular volume fractions increased. Degeneration of cardiomyocytes, such as their wave-like deformation, loss of transverse striation, foci of plasmolysis, and fragmentation of muscle fibers were revealed. In rats treated with glufimet, the structural changes in cardiomyocytes were minimal. Lower vascular plethora was observed; blood vessels were characterized by single stasis and sludge. The cardiomyocyte volume fraction was 9.7% greater than in control animals, while the interstitial and vascular volume fractions were 66.0 and 70.0% smaller, respectively. The animals treated with the RSPU-260 compound had no significant degenerative changes in cardiomyocytes and small vessels similar to the experimental animals injected with glufimet. Mildronate had a less pronounced cardioprotective effect.Conclusion. Administration of new GABA and glutamic acid derivatives to animals with simulated chronic alcohol intoxication leads to improvement of the microstructure in cardiomyocytes compared with control rats. This indicates pronounced cardioprotective effects of the studied neuroactive amino acid derivatives.
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spelling doaj-art-111e2d0d0be5467a8c5cd389fa6a4ef42025-08-20T03:02:04ZengSiberian State Medical University (Tomsk)Бюллетень сибирской медицины1682-03631819-36842023-04-01221738010.20538/1682-0363-2023-1-73-802967Morphological changes in the myocardium of rats with chronic alcohol intoxication after treatment with new GABAand glutamic acid derivativesA. A. Nesterova0I. I. Prokofiev1V. N. Perfilova2O. Yu. Evsyukov3M. V. Kustova4I. N. Tyurenkov5Volgograd State Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityPirogov Russian National Research Medical UniversityVolgograd State Medical UniversityVolgograd State Medical UniversityAim. To study pathohistological changes in the myocardium of rats with chronic alcohol intoxication (CAI) after treatment with a new glutamic acid derivative glufimet (compound RSPU-238) and a new gamma-aminobutyric acid (GABA) derivative (compound RSPU-260).Materials and methods. Experiments were performed on female Wistar rats aged 10 months. The rats were divided into the following groups: group 1 – intact females; group 2 – a control group which included animals after CAI simulated by replacing drinking water with 10% ethanol solution for 24 weeks; groups 3 and 4 – experimental groups, in which females were intraperitoneally administered with glufimet at a dose of 28.7 mg / kg and RSPU260 at a dose of 25 mg / kg once a day for 14 days after cessation of alcohol solution consumption; group 5 – a group of animals receiving a reference listed drug mildronate at a dose of 50 mg / kg according to a regimen similar to that of the studied compounds. Changes in microstructural and morphometric parameters of the left ventricular myocardium were assessed using light microscopy.Results. In animals after CAI, the cardiomyocyte volume fraction decreased, while the interstitial and vascular volume fractions increased. Degeneration of cardiomyocytes, such as their wave-like deformation, loss of transverse striation, foci of plasmolysis, and fragmentation of muscle fibers were revealed. In rats treated with glufimet, the structural changes in cardiomyocytes were minimal. Lower vascular plethora was observed; blood vessels were characterized by single stasis and sludge. The cardiomyocyte volume fraction was 9.7% greater than in control animals, while the interstitial and vascular volume fractions were 66.0 and 70.0% smaller, respectively. The animals treated with the RSPU-260 compound had no significant degenerative changes in cardiomyocytes and small vessels similar to the experimental animals injected with glufimet. Mildronate had a less pronounced cardioprotective effect.Conclusion. Administration of new GABA and glutamic acid derivatives to animals with simulated chronic alcohol intoxication leads to improvement of the microstructure in cardiomyocytes compared with control rats. This indicates pronounced cardioprotective effects of the studied neuroactive amino acid derivatives.https://bulletin.ssmu.ru/jour/article/view/5136chronic alcohol intoxicationcardioprotective effectgaba and glutamic acid derivatives
spellingShingle A. A. Nesterova
I. I. Prokofiev
V. N. Perfilova
O. Yu. Evsyukov
M. V. Kustova
I. N. Tyurenkov
Morphological changes in the myocardium of rats with chronic alcohol intoxication after treatment with new GABAand glutamic acid derivatives
Бюллетень сибирской медицины
chronic alcohol intoxication
cardioprotective effect
gaba and glutamic acid derivatives
title Morphological changes in the myocardium of rats with chronic alcohol intoxication after treatment with new GABAand glutamic acid derivatives
title_full Morphological changes in the myocardium of rats with chronic alcohol intoxication after treatment with new GABAand glutamic acid derivatives
title_fullStr Morphological changes in the myocardium of rats with chronic alcohol intoxication after treatment with new GABAand glutamic acid derivatives
title_full_unstemmed Morphological changes in the myocardium of rats with chronic alcohol intoxication after treatment with new GABAand glutamic acid derivatives
title_short Morphological changes in the myocardium of rats with chronic alcohol intoxication after treatment with new GABAand glutamic acid derivatives
title_sort morphological changes in the myocardium of rats with chronic alcohol intoxication after treatment with new gabaand glutamic acid derivatives
topic chronic alcohol intoxication
cardioprotective effect
gaba and glutamic acid derivatives
url https://bulletin.ssmu.ru/jour/article/view/5136
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