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芦丁对在营养剥夺条件下培养的PC12神经元中氧化性DNA损伤的影响。

Effect of rutin on oxidative DNA damage in PC12 neurons cultured in nutrients deprivation condition.

作者信息

Nassiri-Asl Marjan, Ghorbani Ahmad, Salehisar Sahar, Asadpour Elham, Sadeghnia Hamid Reza

机构信息

Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Iran J Basic Med Sci. 2020 Mar;23(3):390-395. doi: 10.22038/IJBMS.2020.31832.7657.

DOI:10.22038/IJBMS.2020.31832.7657
PMID:32440327
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7229504/
Abstract

OBJECTIVES

Rutin is a flavonoid with potent antioxidant property, which exhibited cytoprotective effects in several models of neuronal injury. This work aimed to examine whether rutin can protect neurons against oxidative DNA damage caused by serum/glucose deprivation (SGD) as an in vitro model of neurodegeneration and ischemia.

MATERIALS AND METHODS

The PC12 cells were cultured for 2 hr in normal culture medium containing different concentrations of rutin or α-tocopherol (positive control) and then further incubated for 12 hr in SGD condition. Then, cell viability, DNA fragmentation, lipid peroxidation, generation of reactive oxygen species (ROS), and the expression of proteins involved in apoptosis were determined.

RESULTS

The SGD condition significantly decreased viability of the cells, which was accompanied by a significant rise in the generation of ROS and lipid peroxidation. Rutin enhanced the viability of PC12 cells in SGD condition and reduced the production of ROS and lipid peroxidation. In addition, rutin decreased DNA damage and inhibited apoptotic cell death by decreasing the levels of proapoptotic proteins (Bax, caspase-3, caspase-9) and increasing the level of anti-apoptotic protein Bcl-2.

CONCLUSION

This study demonstrated that rutin inhibits oxidative DNA damage and neuronal death induced by nutrients deprivation condition. Further studies may warrant the use of rutin as an appropriate neuroprotective agent for ischemic attacks and other neurodegenerative disorders.

摘要

目的

芦丁是一种具有强大抗氧化特性的黄酮类化合物,在多种神经元损伤模型中表现出细胞保护作用。本研究旨在探讨芦丁是否能保护神经元免受血清/葡萄糖剥夺(SGD)所导致的氧化性DNA损伤,SGD是一种用于模拟神经退行性变和缺血的体外模型。

材料与方法

将PC12细胞在含有不同浓度芦丁或α-生育酚(阳性对照)的正常培养基中培养2小时,然后在SGD条件下进一步孵育12小时。随后,测定细胞活力、DNA片段化、脂质过氧化、活性氧(ROS)生成以及凋亡相关蛋白的表达。

结果

SGD条件显著降低了细胞活力,同时伴随着ROS生成和脂质过氧化的显著增加。芦丁提高了SGD条件下PC12细胞的活力,并减少了ROS生成和脂质过氧化。此外,芦丁通过降低促凋亡蛋白(Bax、半胱天冬酶-3、半胱天冬酶-9)的水平并增加抗凋亡蛋白Bcl-2的水平,减少了DNA损伤并抑制了凋亡性细胞死亡。

结论

本研究表明芦丁可抑制营养剥夺条件诱导的氧化性DNA损伤和神经元死亡。进一步的研究可能支持将芦丁用作缺血性发作和其他神经退行性疾病的合适神经保护剂。

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4-((5-(Tert-butyl)-3-chloro-2-hydroxybenzyl) amino)-2-hydroxybenzoic acid protects against oxygen-glucose deprivation/reperfusion injury.
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