Pharmacological correction of the sequelae of acute alcohol-induced myocardial damage with new derivatives of neuroactive amino acids coupled with the blockade of the neuronal NO synthase isoform

Q3 Pharmacology, Toxicology and Pharmaceutics
M. V. Kustova, V. Perfilova, I. I. Prokofiev, Elena A. Musyko, A. S. Kucheryavenko, Elena E. Kusnetsova, Diana E. Tsetsera, I. Tyurenkov
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引用次数: 1

Abstract

Introduction: Acute alcohol intoxication (AAI) induces a number of myocardial disorders, which result in mitochondrial dysfunction in cardiomyocytes, oxidative stress, and decreased cardiac contractility. Nitric oxide produced by the nNOS is one of the major modulators of cardiac activity. New derivatives of GABA (RSPU-260 compound) and glutamate (glufimet) can be potentially regarded as such agents as the interaction between the NO system and the GABA and glutamatergic systems has been proved. Materials and methods: All the studies were performed on female white Wistar rats, aged 10 months, whose weight was 280–320g AAI intoxication was modeled of 32% ethanol (gavage, 4g/kg). Results and discussion: Glufimet and the RSPU-260 compound caused a significant improvement in myocardial contractility, increased oxygen consumption in the V3 state according to Chance, raised the respiratory control ratio and decreased the intensity of LPO intensity. Their effectiveness exceeded that of mildronate, their comparator. nNOS inhibition resulted in a pronounced aggravation of oxidative stress implicated in MDA accumulation in cardiac mitochondria and decreased activity of SOD; myocardial contractility and mitochondrial function indicators did not show a significant difference from the control group. The compounds under study coupled with nNOS inhibition had a cardioprotective effect. Conclusion: Glufimet and the RSPU-260 compound, derivatives of neuroactive amino acids, have a pronounced cardioprotective effect, restrict LPO processes, enhance SOD activity, improve the mitochondrial respiratory function after acute alcohol intoxication when coupled with neuronal NO-synthase inhibition, the expression of which persists after AAI. Graphical abstract:
Pharmacological神经活性氨基酸的新衍生物与神经元NO合成酶亚型的阻断联合纠正急性酒精性心肌损伤的后遗症
引言:急性酒精中毒(AAI)会导致许多心肌疾病,导致心肌细胞线粒体功能障碍、氧化应激和心脏收缩力下降。nNOS产生的一氧化氮是心脏活动的主要调节剂之一。GABA(RSPU-260化合物)和谷氨酸(glufimet)的新衍生物可能被视为NO系统与GABA和谷氨酸能系统之间的相互作用。材料和方法:所有研究均在10个月大的雌性白色Wistar大鼠身上进行,其体重为280–320g,AAI中毒模型为32%乙醇(灌胃,4g/kg)。结果与讨论:Glufimet和RSPU-260复合物可显著改善心肌收缩力,根据Chance增加V3状态下的耗氧量,提高呼吸控制率,降低LPO强度。它们的有效性超过了它们的对照品密膦酸盐。nNOS的抑制导致与心肌线粒体中MDA积累有关的氧化应激的显著加重和SOD活性的降低;心肌收缩力和线粒体功能指标与对照组无显著差异。研究中的化合物结合nNOS抑制具有心脏保护作用。结论:Glufimet和RSPU-260化合物是神经活性氨基酸的衍生物,在急性酒精中毒后与神经元NO合酶抑制结合时,具有显著的心脏保护作用,限制LPO过程,增强SOD活性,改善线粒体呼吸功能,AAI后其表达持续。图形摘要:
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Research Results in Pharmacology
Research Results in Pharmacology Medicine-Pharmacology (medical)
CiteScore
1.50
自引率
0.00%
发文量
32
审稿时长
12 weeks
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