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甲基丙烯酸酯单体的细胞毒性-谷胱甘肽加合物形成的作用。

Cell toxicity of methacrylate monomers-the role of glutathione adduct formation.

机构信息

Department of Clinical Dentistry, University of Bergen, Faculty of Medicine and Dentistry, Bergen, Norway; Nordic Institute of Dental Materials (NIOM), PO Box 3874 Ullevaal stadion, N-0805 Oslo, Norway.

出版信息

J Biomed Mater Res A. 2013 Dec;101(12):3504-10. doi: 10.1002/jbm.a.34652. Epub 2013 Apr 24.

Abstract

Polymer-based dental restorative materials are designed to polymerize in situ. However, the conversion of methacrylate monomer to polymer is never complete, and leakage of the monomer occurs. It has been shown that these monomers are toxic in vitro; hence concerns regarding exposure of patients and dental personnel have been raised. Different monomer methacrylates are thought to cause toxicity through similar mechanisms, and the sequestration of cellular glutathione (GSH) may be a key event. In this study we examined the commonly used monomer methacrylates, 2-hydroxyethylmethacrylate (HEMA), triethylenglycol-dimethacrylate (TEGDMA), bisphenol-A-glycidyl-dimethacrylate (BisGMA), glycerol-dimethacrylate (GDMA) and methyl-methacrylate (MMA). The study aimed to establish monomers' ability to complex with GSH, and relate this to cellular toxicity endpoints. Except for BisGMA, all the monomer methacrylates decreased the GSH levels both in cells and in a cell-free system. The spontaneous formation of methacrylate-GSH adducts were observed for all methacrylate monomers except BisGMA. However, we were not able to correlate GSH depletion and toxic response measured as SDH activity and changes in cell growth pattern. Together, the current study indicates mechanisms other than GSH-binding to be involved in the toxicity of methacrylate monomers.

摘要

基于聚合物的牙科修复材料旨在原位聚合。然而,甲基丙烯酸盐单体向聚合物的转化从未完全完成,单体发生泄漏。已经表明,这些单体在体外具有毒性;因此,人们对患者和牙科医务人员暴露于这些单体的风险表示担忧。不同的单体甲基丙烯酸盐被认为通过类似的机制引起毒性,细胞谷胱甘肽(GSH)的螯合可能是一个关键事件。在这项研究中,我们检查了常用的单体甲基丙烯酸盐,2-羟乙基甲基丙烯酸酯(HEMA)、三乙二醇二甲基丙烯酸酯(TEGDMA)、双酚 A 缩水甘油二甲基丙烯酸酯(BisGMA)、甘油二甲基丙烯酸酯(GDMA)和甲基丙烯酸甲酯(MMA)。该研究旨在确定单体与 GSH 络合的能力,并将其与细胞毒性终点相关联。除了 BisGMA 之外,所有单体甲基丙烯酸盐都降低了细胞和无细胞体系中 GSH 的水平。除了 BisGMA 之外,所有单体甲基丙烯酸盐都观察到了甲基丙烯酸盐-GSH 加合物的自发形成。然而,我们无法将 GSH 耗竭与作为 SDH 活性和细胞生长模式变化测量的毒性反应相关联。总之,目前的研究表明,与 GSH 结合以外的机制参与了甲基丙烯酸盐单体的毒性。

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