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辅酶 Q10 对敌敌畏诱导的大鼠认知障碍和神经退行性变的保护作用。

Protective efficacy of coenzyme Q10 against DDVP-induced cognitive impairments and neurodegeneration in rats.

机构信息

Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.

出版信息

Neurotox Res. 2012 May;21(4):345-57. doi: 10.1007/s12640-011-9289-0. Epub 2011 Nov 15.

DOI:10.1007/s12640-011-9289-0
PMID:22083459
Abstract

The present study was carried out to elucidate the effects of coenzyme Q(10) (CoQ(10)) against cognitive impairments induced by dichlorvos (DDVP). We have previously shown organophosphate, DDVP-induced impairments in neurobehavioral indices viz. rota rod, passive avoidance, and water maze tests. In addition to this, we have also reported that chronic DDVP exposure leads to decreased mitochondrial electron transfer activities of cytochrome oxidase along with altered mitochondrial complexes I-III activity. Administration of CoQ(10) (4.5 mg/kg, i.p. for 12 weeks prior to DDVP administration daily) to DDVP-treated rats improved cognitive performance in passive avoidance task and Morris water maze test. Furthermore, CoQ(10) treatment also reduced oxidative stress (as evident by reduced malondialdehyde, decreased ROS and increased Mn-SOD activity) in DDVP-treated rats' hippocampus region, along with enhanced activity of complexes I-III and complex IV. Electron microscope studies of rat hippocampus mitochondria revealed that CoQ(10) administration leads to near normal physiology of mitochondria with well-defined cristae compared with DDVP-treated animals where enlarged mitochondria with distorted cristae are observed. CoQ(10) administration also attenuated neuronal damage in hippocampus as evident from histopathological studies. These results demonstrate the beneficial effects of CoQ(10) against organophosphate-induced cognitive impairments and hippocampal neuronal degeneration.

摘要

本研究旨在阐明辅酶 Q(10)(CoQ(10))对二氯氧磷(DDVP)诱导的认知障碍的作用。我们之前已经证明,有机磷化合物 DDVP 会损害神经行为指数,如转棒、被动回避和水迷宫测试。除此之外,我们还报告说,慢性 DDVP 暴露会导致细胞色素氧化酶的线粒体电子传递活性降低,同时改变线粒体复合物 I-III 的活性。DDVP 处理大鼠腹腔注射 CoQ(10)(4.5mg/kg,每天 12 周,在 DDVP 处理前)可改善被动回避任务和 Morris 水迷宫测试中的认知表现。此外,CoQ(10) 处理还降低了 DDVP 处理大鼠海马区的氧化应激(如丙二醛减少、ROS 减少和 Mn-SOD 活性增加),并增强了复合物 I-III 和复合物 IV 的活性。大鼠海马线粒体的电子显微镜研究表明,CoQ(10) 给药可使线粒体的生理状态接近正常,嵴定义明确,而 DDVP 处理的动物则观察到线粒体增大和嵴扭曲。CoQ(10) 给药还减轻了海马中的神经元损伤,这从组织病理学研究中可以明显看出。这些结果表明 CoQ(10) 对有机磷诱导的认知障碍和海马神经元变性具有有益作用。

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