Triethylene glycol dimethacrylate impairs bioenergetic functions and induces oxidative stress in mitochondria via inhibiting respiratory Complex I

Objectives. Earlier studies demonstrated that dental resin monomers lower cellular viability and provoke oxidative stress. Reactive oxygen species (ROS) formation has a key role in triethylene glycol dimethacrylate (TEGDMA) induced adverse reactions. In the present study the effects of TEGDMA on mitochondrial functions were investigated to identify a direct molecular target for cytotoxicity. Methods. Mitochondria were isolated from guinea pig brain. The most important bioenergetic parameters, oxygen consumption, membrane potential (Delta psi(m)), and ATP production were assessed. Mitochondrial H2O2 production and elimination and the NAD(P)H level reported on redox balance. Results. Mitochondria were supported with respiratory substrates to be oxidized by either Complex I (CI) or Complex II (CII). Delta psi(m) was depolarized, respiration and ATP production was greatly diminished when applying CI substrates in the presence of TEGDMA. The same parameters remained essentially unaffected when CII substrate plus TEGDMA were applied. H2O2 production by mitochondria was significantly stimulated by TEGDMA in the presence of CI substrates. In the presence of TEGDMA mitochondrial elimination of exogenous H2O2 was impaired. When CII substrate supported the mitochondria in the absence of ADP the H2O2 generation was decreased. NADH autofluorescence results also demonstrated the inhibitory effect of TEGDMA on CI activity. Significance. TEGDMA inhibits CI in the respiratory chain, which explains effects induced by TEGDMA on redox homeostasis, apoptotic and necrotic cell deaths described in previous studies. Identification of the molecular target of TEGDMA may influence the development of relevant biomaterials and may induce new therapeutic strategies to control the adverse effects of resin monomers. (C) 2018 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).