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.