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杂化儿茶素二氧化硅纳米颗粒对原代神经元细胞中铜(II)毒性和形态损伤的影响

Hybrid catechin silica nanoparticle influence on Cu(II) toxicity and morphological lesions in primary neuronal cells.

作者信息

Halevas E, Nday C M, Salifoglou A

机构信息

Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.

Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.

出版信息

J Inorg Biochem. 2016 Oct;163:240-249. doi: 10.1016/j.jinorgbio.2016.04.017. Epub 2016 Apr 21.

Abstract

Morphological alterations compromising inter-neuronal connectivity may be directly linked to learning-memory deficits in Central Nervous System neurodegenerative processes. Cu(II)-mediated oxidative stress plays a pivotal role in regulating redox reactions generating reactive oxygen species (ROS) and reactive nitrogen species (RNS), known contributors to Alzheimer's disease (AD) pathology. The antioxidant properties of flavonoid catechin have been well-documented in neurodegenerative processes. However, the impact that catechin encapsulation in nanoparticles may have on neuronal survival and morphological lesions has been poorly demonstrated. To investigate potential effects of nano-encapsulated catechin on neuronal survival and morphological aberrations in primary rat hippocampal neurons, poly(ethyleneglycol) (PEG) and cetyltrimethylammonium bromide (CTAB)-modified silica nanoparticles were synthesized. Catechin was loaded on silica nanoparticles in a concentration-dependent fashion, and release studies were carried out. Further physicochemical characterization of the new nano-materials included elemental analysis, particle size, z-potential, FT-IR, Brunauer-Emmett-Teller (BET), thermogravimetric (TGA), and scanning electron microscopy (SEM) analysis in order to optimize material composition linked to the delivery of loaded catechin in the hippocampal cellular milieu. The findings reveal that, under Cu(II)-induced oxidative stress, the loading ability of the PEGylated/CTAB silica nanoparticles was concentration-dependent, based on their catechin release profile. The overall bio-activity profile of the new hybrid nanoparticles a) denoted their enhanced protective activity against oxidative stress and hippocampal cell survival compared to previously reported quercetin, b) revealed that morphological lesions affecting neuronal integrity can be counterbalanced at high copper concentrations, and c) warrants in-depth perusal of molecular events underlying neuronal function and degeneration, collectively linked to preventive nanotechnology in neurodegeneration.

摘要

损害神经元间连接性的形态学改变可能与中枢神经系统神经退行性病变过程中的学习记忆缺陷直接相关。铜(II)介导的氧化应激在调节产生活性氧(ROS)和活性氮(RNS)的氧化还原反应中起关键作用,而ROS和RNS是阿尔茨海默病(AD)病理的已知促成因素。类黄酮儿茶素的抗氧化特性在神经退行性病变过程中已有充分记录。然而,儿茶素包裹在纳米颗粒中对神经元存活和形态损伤的影响尚未得到充分证明。为了研究纳米包裹儿茶素对原代大鼠海马神经元存活和形态异常的潜在影响,合成了聚乙二醇(PEG)和十六烷基三甲基溴化铵(CTAB)修饰的二氧化硅纳米颗粒。儿茶素以浓度依赖的方式负载在二氧化硅纳米颗粒上,并进行了释放研究。对新型纳米材料的进一步物理化学表征包括元素分析、粒径、z电位、傅里叶变换红外光谱(FT-IR)、布鲁诺尔-埃米特-特勒(BET)、热重分析(TGA)和扫描电子显微镜(SEM)分析,以优化与负载儿茶素在海马细胞环境中的递送相关的材料组成。研究结果表明,在铜(II)诱导的氧化应激下,基于其儿茶素释放曲线,聚乙二醇化/CTAB二氧化硅纳米颗粒的负载能力是浓度依赖的。新型杂化纳米颗粒的总体生物活性概况:a)表明与先前报道的槲皮素相比,它们对氧化应激和海马细胞存活具有增强的保护活性;b)表明在高铜浓度下,影响神经元完整性的形态损伤可以得到平衡;c)需要深入研究与神经退行性病变中的预防性纳米技术相关的神经元功能和退化背后的分子事件。

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