title: TEGDMA-induced toxicity in human fibroblasts is associated with early and drastic glutathione depletion with subsequent production of oxygen reactive species.
abstract: Triethylene glycol dimethacrylate (TEGDMA) is a dentin-bonding agent and a major component of various dental restorative biomaterials. TEGDMA monomers are released from dental resins and induce dental pulp inflammation and necrosis. In this study, we have investigated the mechanism of TEGDMA-induced cytotoxicity of fibroblasts. Treatment of cultured human gingival and pulpal fibroblasts with 0.1-3 mM of TEGDMA for 24 h induced a concentration-dependent and variable cytotoxic effect. Fifty percent of toxicity (TC(50)) was obtained with 1.2 +/- 0.9 and 2.6 +/- 1.1 mM of TEGDMA for gingival and pulpal fibroblasts, respectively. Moreover, TEGDMA-induced cytotoxicity was associated with an early and drastic depletion of cellular glutathione (GSH), which started at 15-30 min and was almost complete at 4-6 h. Antioxidants, such as Trolox (0.01 mM), ascorbate (0.2 mM), and N-acetylcysteine (NAC) (5 mM) prevented the TEGDMA-induced cytotoxicity while GSH depletion was partially inhibited. Finally, a late production of reactive oxygen species (ROS) occurred in fibroblasts treated with TEGDMA for 3-4 h, as determined by 2',7'-dichlorofluorescein fluorescence, and was completely inhibited by Trolox (5 microM). The data show that TEGDMA induced a drastic GSH depletion followed by production of ROS, which may contribute to the toxicity of gingival and pulpal fibroblasts. Antioxidants, such as NAC, ascorbate, and particularly Trolox, appear useful in preventing cell damage mediated by resin-containing dental restorative materials.
authors.affiliation: Faculté de Chirurgie Dentaire, Université René Descartes, 1 rue Maurice Arnoux, 92120 Montrouge, France. lenastan@hotmail.com
authors.forename: Lena
authors.initials: L
authors.lastname: Stanislawski
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lefeuvre
authors.forename: Katia
authors.initials: K
authors.lastname: Bourd
authors.forename: Esmat
authors.initials: E
authors.lastname: Soheili-Majd
authors.forename: Michel
authors.initials: M
authors.lastname: Goldberg
authors.forename: Axel
authors.initials: A
authors.lastname: Périanin
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D011092:Polyethylene Glycols / Q000633:toxicity*; D011109:Polymethacrylic Acids / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D011109:Polymethacrylic Acids; D017382:Reactive Oxygen Species; C020946:triethylene glycol dimethacrylate; D011092:Polyethylene Glycols; D005978:Glutathione