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

Krisztina Mikulás, P. Hermann, I. Gera, Timea Komlódi, Gergő Horváth, A. Ambrus, L. Tretter

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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 (ΔΨm), 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). ΔΨm 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.

Original languageEnglish
JournalDental Materials
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Electron Transport Complex I
Mitochondria
Oxidative stress
Glycols
Energy Metabolism
Oxidative Stress
Substrates
Adenosinetriphosphate
NAD
Oxidation-Reduction
Resins
Adenosine Triphosphate
Monomers
triethylene glycol dimethacrylate
Synthetic Resins
Administrative data processing
Oxygen
Biocompatible Materials
Cell death
Cytotoxicity

Keywords

  • ATP production
  • Cytotoxicity
  • Dental resin monomer TEGDMA
  • Hydrogen peroxide
  • Oxidative stress
  • Reactive oxygen species
  • Respiration
  • Respiratory Complex I

ASJC Scopus subject areas

  • Materials Science(all)
  • Dentistry(all)
  • Mechanics of Materials

Cite this

@article{10135f7ed9fc4e10a95b2bc831af8786,
title = "Triethylene glycol dimethacrylate impairs bioenergetic functions and induces oxidative stress in mitochondria via inhibiting respiratory Complex I",
abstract = "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 (ΔΨm), 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). ΔΨm 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.",
keywords = "ATP production, Cytotoxicity, Dental resin monomer TEGDMA, Hydrogen peroxide, Oxidative stress, Reactive oxygen species, Respiration, Respiratory Complex I",
author = "Krisztina Mikul{\'a}s and P. Hermann and I. Gera and Timea Koml{\'o}di and Gergő Horv{\'a}th and A. Ambrus and L. Tretter",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.dental.2018.03.012",
language = "English",
journal = "Dental Materials",
issn = "0109-5641",
publisher = "Elsevier Science",

}

TY - JOUR

T1 - Triethylene glycol dimethacrylate impairs bioenergetic functions and induces oxidative stress in mitochondria via inhibiting respiratory Complex I

AU - Mikulás, Krisztina

AU - Hermann, P.

AU - Gera, I.

AU - Komlódi, Timea

AU - Horváth, Gergő

AU - Ambrus, A.

AU - Tretter, L.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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 (ΔΨm), 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). ΔΨm 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.

AB - 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 (ΔΨm), 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). ΔΨm 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.

KW - ATP production

KW - Cytotoxicity

KW - Dental resin monomer TEGDMA

KW - Hydrogen peroxide

KW - Oxidative stress

KW - Reactive oxygen species

KW - Respiration

KW - Respiratory Complex I

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U2 - 10.1016/j.dental.2018.03.012

DO - 10.1016/j.dental.2018.03.012

M3 - Article

C2 - 29673707

AN - SCOPUS:85045452152

JO - Dental Materials

JF - Dental Materials

SN - 0109-5641

ER -