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.

Q3 Biochemistry, Genetics and Molecular Biology Biomeditsinskaya khimiya Pub Date : 2023-04-01 DOI:10.18097/PBMC20236902112
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
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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.

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iNOS抑制在新型GABA和谷氨酸衍生物对大鼠急性酒精性心肌损伤模型心脏保护作用机制中的作用。
在选择性阻断诱导型no合成酶(iNOS)的条件下,研究了谷氨酸(glufimet)和GABA (mefargin)的新衍生物对急性酒精中毒(AAI)大鼠的心脏保护作用。在运动试验(按体积负荷、肾上腺素反应性试验、等长运动)中,AAI诱导心肌收缩功能明显下降,导致线粒体功能障碍和心脏细胞脂质过氧化(LPO)过程增加。在iNOS抑制和AAI过程中,一氧化氮生成的减少改善了线粒体的呼吸功能,降低了LPO产物的水平,增加了线粒体超氧化物歧化酶的活性。这导致心肌收缩力增加。所研究的化合物,glufimet和mefargin,在心肌收缩和舒张率,左心室压,以及减少NO的产生方面有统计学意义的增加。这伴随着LPO过程强度的降低和呼吸控制比(RCR)的增加,反映了呼吸链复合物I和II激活过程中呼吸和磷酸化过程之间的耦合。在选择性阻断iNOS和施用所研究物质期间,NO浓度的下降比没有阻断酶的情况下更不明显。这表明神经活性氨基酸的新衍生物对一氧化氮系统的推测作用。
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来源期刊
Biomeditsinskaya khimiya
Biomeditsinskaya khimiya Biochemistry, 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).
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