TEGDMA induces mitochondrial damage and oxidative stress in human gingival fibroblasts.
Free monomers including triethylene glycol dimethacrylate (TEGDMA) are released by resin composite. Recent studies in vitro have demonstrated that TEGDMA induced GSH depletion and production of radical oxygen species (ROS) in human gingival fibroblasts (HGF) but the exact mechanism of these events remains unclear. Our purpose is to investigate the origin of ROS production. TEGDMA induces a rapid (within 30 min) and drastic depletion of ATP concomitant with the GSH depletion. After 3h incubation, TEGDMA induced an increase of lipid peroxidation associated with LDH leakage. Our data also showed that TEGDMA produced damage at mitochondrial level. This is demonstrated by the collapse of mitochondrial membrane potential (MMP) in HGF treated with TEGDMA. The protective effect of carbonylcyanide m-chlorophenylhydrazone (CCCP), an uncoupler of oxidative phosphorylation on lipid peroxidation and LDH leakage suggests that mitochondria can be implicated in these events. Trolox, a soluble derivative of Tocopherol, weakly prevents ATP but not GSH depletion and totally protects the cells against lipid peroxidation, MMP collapse and cell death. Thus, the present results suggest that TEGDMA induces lipid peroxidation and mitochondrial damage, which contribute to cell death.
Lefeuvre
Mathieu
M
Faculté de Chirurgie Dentaire, Université René Descartes, 1 rue Maurice Arnoux, 92120 Montrouge, France.
Amjaad
Wafaa
W
Goldberg
Michel
M
Stanislawski
Lena
L
D000255:Adenosine Triphosphate / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D003188:Composite Resins / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000166:cytology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011109:Polymethacrylic Acids / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D002839:Chromans; D003188:Composite Resins; D011109:Polymethacrylic Acids; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C020946:triethylene glycol dimethacrylate; D011092:Polyethylene Glycols; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid