暴露于邻苯二甲酸二乙酯的大鼠肝脏线粒体中的自由基过程

O. Ketsa, A. P. Husliakova, M. Marchenko
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引用次数: 0

摘要

邻苯二甲酸二乙酯(DEF)是一种合成化学品,广泛用作个人护理产品和药品的增塑剂和添加剂。长期低剂量接触这种异生物会导致人体摄入高剂量的邻苯二甲酸二乙酯。迄今为止,有关 DEF 对肝细胞中自由基过程的影响(DEF 在肝细胞中不仅被代谢,还可能产生促氧化作用)的研究仍然有限。我们的研究目的是确定 ROS 的形成、蛋白质氧化修饰(OMP)的强度以及暴露于过硫酸二乙酯的大鼠肝组织线粒体部分的蛋白质分解活性。实验白种大鼠分为三组:I 组--完好无损的动物(对照组),II 组和 III 组--连续三周口服 DEF 的大鼠,剂量分别为 2.5 毫克/千克体重和 5.4 毫克/千克体重,该剂量反映了人类摄入的剂量水平。给药后第 14 天和第 21 天,动物被安乐死。从大鼠肝脏中分离出线粒体部分,并测定超氧化物和羟自由基、蛋白质羰基衍生物、SH-基团和希夫碱的含量。在血红蛋白裂解试验中对蛋白质分解活性进行了评估。结果表明,大鼠肝脏线粒体中生成 ROS 和加强 OMP 的 DEF 剂量为 2.5 毫克/千克,只有在长期服用 21 天后才会开始,而服用 5.4 毫克/千克的 DEF 会在第 14 天导致这些过程加强,并在第 21 天进一步扩大。研究发现,线粒体组分中蛋白水解酶的活性取决于 DEF 诱导的 OMP 的程度,当 OMP 轻微增强时,蛋白水解酶的活性增强,但当蛋白质自由基氧化显著增强时,蛋白水解酶的活性降低。关键词:羰基衍生物、邻苯二甲酸二乙酯、肝脏、线粒体组分、蛋白水解酶、ROS、SH-基团
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Free radical processes in the liver mitochondria of rats exposed to diethyl phthalate
Diethyl phthalate (DEF) is a synthetic chemical widely used as plasticizer and additive in personal care and pharmaceutical products. Low-dose exposure to this xenobiotic over a long period contributes to its intake into the human body in a high doses. To date, studies of DEF influence on free radical processes in liver cells, in which it is not only metabolized but can also have a prooxidant effect, remain limited. The aim of our research was to determine ROS formation, the intensity of oxidative modification of proteins (OMP) and proteolytic activity in the mitochondrial fraction of liver tissue of rats exposed to diethyl phtalate. The experimental white outbred rats were divided into three groups: I – intact animals (control), II and III – rats administered DEF orally for three weeks at a doses that reflect the dose levels received by humans, namely 2.5 and 5.4 mg/kg b.w. respectively. The animals were euthanized on the 14th and 21st day after xenobiotic administration. The mitochondrial fraction from the rat liver was isolated and the level of superoxide and hydroxyl radicals, protein carbonyl derivatives, SH-groups and Schiff bases was determined. Proteolytic activity was assessed in the test of hemoglobin cleavage. It was shown that administration of DEF in a dose of 2.5 mg/kg initiated ROS generation and OMP intensification in the rat liver mitochondria only with prolonged administration for 21 days, whereas its administration in a dose of 5.4 mg/kg led to intensification of these processes already on day 14th followed by further amplification on day 21st. The activity of proteolytic enzymes in the mitochondrial fraction was found to be depended on the degree of DEF–induced OMP and was increased with minor OMP intensification but decreased with significant intensification of proteins free radical oxidation. Keywords: carbonyl derivatives, diethyl phthalate, liver, mitochondrial fraction, proteolytic enzymes, ROS, SH-groups
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