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卡波氯铵能够调节慢性酒精中毒中的线粒体通透性转换孔的开放。

Carbenoxolon Is Capable to Regulate the Mitochondrial Permeability Transition Pore Opening in Chronic Alcohol Intoxication.

机构信息

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, 142290 Moscow, Russia.

出版信息

Int J Mol Sci. 2021 Sep 23;22(19):10249. doi: 10.3390/ijms221910249.

Abstract

BACKGROUND

carbenoxolone, which is a derivative of glyceretic acid, is actively used in pharmacology for the treatment of diseases of various etiologies. In addition, we have shown carbenoxolone as an effective inducer of mitochondrial permeability transition pore in rat brain and liver mitochondria.

METHODS

in the course of this work, comparative studies were carried out on the effect of carbenoxolone on the parameters of mPTP functioning in mitochondria isolated from the liver of control and alcoholic rats.

RESULTS

within the framework of this work, it was found that carbenoxolone significantly increased its effect in the liver mitochondria of rats with chronic intoxication. In particular, this was expressed in a reduction in the lag phase, a decrease in the threshold calcium concentration required to open a pore, an acceleration of high-amplitude cyclosporin-sensitive swelling of mitochondria, as well as an increase in the effect of carbenoxolone on the level of mitochondrial membrane-bound proteins. Thus, as a result of the studies carried out, it was shown that carbenoxolone is involved in the development/modulation of alcohol tolerance and dependence in rats.

摘要

背景

卡波氯铵是甘油酸的衍生物,在药理学中被广泛用于治疗各种病因的疾病。此外,我们已经证明卡波氯铵可有效诱导大鼠脑和肝线粒体中的线粒体通透性转换孔。

方法

在这项工作的过程中,对卡波氯铵对来自对照和酒精中毒大鼠肝脏线粒体中 mPTP 功能参数的影响进行了比较研究。

结果

在这项工作的框架内,发现卡波氯铵在慢性中毒大鼠的肝线粒体中显著增加了其作用。具体表现为潜伏期缩短,打开孔所需的阈钙离子浓度降低,线粒体高幅度环孢素敏感肿胀加速,以及卡波氯铵对线粒体膜结合蛋白水平的影响增加。因此,通过进行的研究表明,卡波氯铵参与了大鼠对酒精的耐受性和依赖性的发展/调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/857f/8549702/d3b3f63608dc/ijms-22-10249-g001.jpg

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