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 (ΔΨ_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). ΔΨ_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.