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槲皮素在慢性毒死蜱暴露于大鼠时氧化诱导的凋亡事件中发挥保护作用。

Quercetin plays protective role in oxidative induced apoptotic events during chronic chlorpyrifos exposure to rats.

机构信息

Department of Biophysics, Panjab University, Chandigarh, India.

Centre for Nuclear Medicine, Panjab University, Chandigarh, India.

出版信息

J Biochem Mol Toxicol. 2019 Aug;33(8):e22341. doi: 10.1002/jbt.22341. Epub 2019 Apr 16.

DOI:10.1002/jbt.22341
PMID:30990955
Abstract

Chlorpyrifos (CPF), an organophosphate insecticide has a wider application throughout the world to protect agricultural crops and vegetables from insects. Polyphenolic compounds are considered as beneficial against toxicities induced by organophosphates. The present study was conducted to understand the neuroprotective role of quercetin in chlorpyrifos-induced apoptotic events in rats. Twenty-four male Sprague Dawley rats weighing 170 to 200 g were divided into four groups viz: Control, chlorpyrifos treated (13.5 mg/kg body wt. alternate day), quercetin treated (50 mg/kg body wt. every day) and combined chlorpyrifos + quercetin treated. All the treatments were carried out for a total duration of 60 days. Protein carbonyl content and acetylcholinesterase activity were estimated in serum along with cerebrum and cerebellum to ascertain neurotoxicity. Further, for appraisal of neurodegeneration as a consequence of apoptosis, protein expressions of Bcl-2, Bax, cytochrome c, caspase-8, and caspase-9 were assessed. The results showed that protein carbonyl contents were markedly increased in both serum and brain tissues (cerebrum and cerebellum) of chlorpyrifos-treated rats when compared with control group and were appreciably improved upon simultaneous supplementation with quercetin. Further, chlorpyrifos treatment revealed a significant decrease in the enzyme activity of acetylcholinesterase in serum as well as in cerebrum and cerebellum, which however was increased upon concomitant treatment with quercetin. In chlorpyrifos-treated animals, we have observed a significant decrease in the protein expression level of Bcl-2, but a remarkable increase in the expression levels of Bax, cytochrome c, caspase-8, and caspase-9 in both cerebrum and cerebellum. Interestingly, when chlorpyrifos-treated animals were supplemented with quercetin, a significant increase in the expression of Bcl-2 and an appreciable decline in the expression levels of Bax, cytochrome c, caspase-8, and caspase-9 was observed. In conclusion, the present study advocates that quercetin may prove to be a useful candidate in containing the oxidative-induced apoptotic events during chlorpyrifos exposure.

摘要

毒死蜱(CPF)是一种有机磷杀虫剂,在世界范围内广泛应用于保护农作物和蔬菜免受昆虫侵害。多酚类化合物被认为对有机磷引起的毒性具有有益作用。本研究旨在了解槲皮素在大鼠体内毒死蜱诱导的凋亡事件中的神经保护作用。24 只雄性 Sprague Dawley 大鼠,体重 170-200g,分为四组:对照组、毒死蜱处理组(13.5mg/kg 体重,隔日)、槲皮素处理组(50mg/kg 体重,每天)和联合毒死蜱+槲皮素处理组。所有处理均持续 60 天。测定血清及大脑和小脑的蛋白羰基含量和乙酰胆碱酯酶活性,以确定神经毒性。此外,为了评估凋亡引起的神经退行性变,评估了 Bcl-2、Bax、细胞色素 c、caspase-8 和 caspase-9 的蛋白表达。结果表明,与对照组相比,毒死蜱处理组大鼠血清及脑组织(大脑和小脑)中的蛋白羰基含量明显增加,同时补充槲皮素可显著改善。此外,毒死蜱处理导致血清以及大脑和小脑中的乙酰胆碱酯酶活性显著降低,但同时用槲皮素处理可使其增加。在毒死蜱处理的动物中,我们观察到 Bcl-2 的蛋白表达水平显著降低,但 Bax、细胞色素 c、caspase-8 和 caspase-9 的表达水平在大脑和小脑中显著增加。有趣的是,当用槲皮素补充毒死蜱处理的动物时,Bcl-2 的表达显著增加,而 Bax、细胞色素 c、caspase-8 和 caspase-9 的表达水平明显下降。综上所述,本研究表明,槲皮素可能是一种有用的候选药物,可用于控制接触毒死蜱时氧化诱导的凋亡事件。

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