The role of iNOS inhibition in the mechanism of the cardioprotective effect of new GABA and glutamic acid derivatives in the model of acute alcoholic myocardial injury in rats.
M V Kustova, I I Prokofiev, V N Perfilova, E A Muzyko, V E Zavadskaya, S V Varlamova, A S Kucheryavenko, I N Tyurenkov, O S Vasilyeva
{"title":"The role of iNOS inhibition in the mechanism of the cardioprotective effect of new GABA and glutamic acid derivatives in the model of acute alcoholic myocardial injury in rats.","authors":"M V Kustova, I I Prokofiev, V N Perfilova, E A Muzyko, V E Zavadskaya, S V Varlamova, A S Kucheryavenko, I N Tyurenkov, O S Vasilyeva","doi":"10.18097/PBMC20236902112","DOIUrl":null,"url":null,"abstract":"<p><p>The cardioprotective effects of new derivatives of glutamic acid (glufimet) and GABA (mefargin) were studied in rats exposed to acute alcohol intoxication (AAI) under conditions of selective blockade of inducible NO-synthase (iNOS). AAI induced a pronounced decrease in the contractile function of the myocardium during exercise tests (load by volume, test for adrenoreactivity, isometric exercise), caused mitochondrial dysfunction and increased processes of lipid peroxidation (LPO) in heart cells. A decrease in NO production during iNOS inhibition and AAI improved the respiratory function of mitochondria, a decreased the level of LPO products, and increased mitochondrial superoxide dismutase activity of heart cells. This led to an increase in myocardial contractility. The studied compounds, glufimet and mefargin, caused a statistically significant increase in the rates of myocardial contraction and relaxation, left ventricular pressure, and also reduced NO production. This was accompanied by a decrease in the intensity of LPO processes and an increase in the respiratory control ratio (RCR), reflecting the coupling between respiration and phosphorylation processes during activation of the respiratory chain complexes I and II. The decrease in NO concentration during selective blockade of iNOS and administration of the studied substances was less pronounced than without blockade of the enzyme. This suggests the putative effect of new derivatives of neuroactive amino acids on the NO system.</p>","PeriodicalId":8889,"journal":{"name":"Biomeditsinskaya khimiya","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomeditsinskaya khimiya","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.18097/PBMC20236902112","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0
Abstract
The cardioprotective effects of new derivatives of glutamic acid (glufimet) and GABA (mefargin) were studied in rats exposed to acute alcohol intoxication (AAI) under conditions of selective blockade of inducible NO-synthase (iNOS). AAI induced a pronounced decrease in the contractile function of the myocardium during exercise tests (load by volume, test for adrenoreactivity, isometric exercise), caused mitochondrial dysfunction and increased processes of lipid peroxidation (LPO) in heart cells. A decrease in NO production during iNOS inhibition and AAI improved the respiratory function of mitochondria, a decreased the level of LPO products, and increased mitochondrial superoxide dismutase activity of heart cells. This led to an increase in myocardial contractility. The studied compounds, glufimet and mefargin, caused a statistically significant increase in the rates of myocardial contraction and relaxation, left ventricular pressure, and also reduced NO production. This was accompanied by a decrease in the intensity of LPO processes and an increase in the respiratory control ratio (RCR), reflecting the coupling between respiration and phosphorylation processes during activation of the respiratory chain complexes I and II. The decrease in NO concentration during selective blockade of iNOS and administration of the studied substances was less pronounced than without blockade of the enzyme. This suggests the putative effect of new derivatives of neuroactive amino acids on the NO system.
Biomeditsinskaya khimiyaBiochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
1.30
自引率
0.00%
发文量
49
期刊介绍:
The aim of the Russian-language journal "Biomeditsinskaya Khimiya" (Biomedical Chemistry) is to introduce the latest results obtained by scientists from Russia and other Republics of the Former Soviet Union. The Journal will cover all major areas of Biomedical chemistry, including neurochemistry, clinical chemistry, molecular biology of pathological processes, gene therapy, development of new drugs and their biochemical pharmacology, introduction and advertisement of new (biochemical) methods into experimental and clinical medicine etc. The Journal also publish review articles. All issues of journal usually contain invited reviews. Papers written in Russian contain abstract (in English).