Engelmann J, Leyhausen G, Leibfritz D, Geurtsen W
Department of Conservative Dentistry and Periodontology, Medical University Hannover, D-30625 Hannover, Germany.
J Biomed Mater Res. 2002;63(6):746-51. doi: 10.1002/jbm.10465.
Previous studies revealed that primarily small and relatively hydrophilic comonomers, such as TEGDMA, leach out of resin-based restorative materials into aqueous media. Subsequently, these compounds may cause detrimental reactions with intracellular metabolic systems. The present experiments attempted to elucidate the interactions of TEGDMA with the important intracellular reducing agent glutathione (GSH). The influence of various concentrations of TEGDMA (0.5-7.5 mM) on viability and intracellular GSH concentration of primary human gingival fibroblasts was determined by means of a fluorescence assay (monobromobimane) performed in microtiter plates. Cells were treated with TEDGMA between 2 and 24 h. The incubation of fibroblasts with TEGDMA even at subtoxic concentrations quickly decreased the intracellular glutathione level to 30-50% of controls within the first 2-6 hours. However, no simultaneous adverse effect on cell viability was found. Longer incubation periods up to 24 h caused a regulatory reincrease at TEGDMA concentrations <or= 2.5 mM, whereas higher concentrations resulted in a continuous depletion of glutathione concentration concomitant with a significant decrease of cell viability. Because glutathione plays an important role in protection and detoxification processes as well in the regulation of cell death, the early and extensive depletion of the intracellular glutathione pool due to TEGDMA may significantly contribute to the cytotoxic potency of this compound.
先前的研究表明，主要是一些小的且相对亲水性的共聚单体，如双甲基丙烯酸三乙二醇酯（TEGDMA），会从树脂基修复材料中渗出到水性介质中。随后，这些化合物可能会与细胞内代谢系统发生有害反应。本实验试图阐明TEGDMA与重要的细胞内还原剂谷胱甘肽（GSH）之间的相互作用。通过在微量滴定板中进行的荧光测定法（单溴代双马来酰亚胺），测定了不同浓度的TEGDMA（0.5 - 7.5 mM）对原代人牙龈成纤维细胞活力和细胞内GSH浓度的影响。细胞用TEGDMA处理2至24小时。即使在亚毒性浓度下，将成纤维细胞与TEGDMA一起孵育，在最初的2至6小时内，细胞内谷胱甘肽水平也会迅速降至对照水平的30% - 50%。然而，未发现对细胞活力有同时产生的不利影响。长达24小时的更长孵育期导致在TEGDMA浓度≤2.5 mM时出现调节性再增加，而更高浓度则导致谷胱甘肽浓度持续耗竭，同时细胞活力显著下降。由于谷胱甘肽在保护和解毒过程以及细胞死亡调节中起着重要作用，TEGDMA导致的细胞内谷胱甘肽池的早期和广泛耗竭可能会显著促成该化合物的细胞毒性。
