Alterations of energy metabolism and glutathione levels of HL-60 cells induced by methacrylates present in composite resins

J Dent. 2007 Mar;35(3):187-94. doi: 10.1016/j.jdent.2006.07.008. Epub 2006 Sep 18.

Abstract

Objectives: Methacrylic compounds such as 2-hydroxyethyl methacrylate (HEMA), triethylene glycol dimethacrylate (TEGDMA) and bisphenol A glycerolate (1 glycerol/phenol) dimethacrylate (Bis-GMA) are largely present in auto- or photopolymerizable composite resins. Since the polymerization reaction is never complete, these molecules are released into the oral cavity tissues and biological fluids where they could cause local adverse effects. The aim of this work was to verify the hypothesis that the biological effects of HEMA, TEGDMA and Bis-GMA - at a non-cytotoxic concentration - depend on the interaction with mitochondria and exert consequent alterations of energy metabolism, GSH levels and the related pathways in human promyelocytic cell line (HL-60).

Methods: The biological effects of methacrylic monomers were determined by analyzing the following parameters: GSH concentration, glucose-6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR) activity, oxygen and glucose consumption and lactate production along with cell differentiation and proliferation.

Results: All monomers induced both cellular differentiation and decrease in oxygen consumption. Cells treated with TEGDMA and Bis-GMA showed a significant enhancement of glucose consumption and lactate production. TEGDMA and HEMA induced GSH depletion stimulating G6PDH and GR activity.

Conclusions: All the monomers under study affect the metabolism of HL-60 cells and show differentiating activity. Since alterations in cellular metabolism occurred at compound concentrations well below cytotoxic levels, the changes in energy metabolism and glutathione redox balance could be considered as potential mechanisms for inducing clinical and sub-clinical adverse effects and thus providing useful parameters when testing biocompatibility of dental materials.

MeSH terms

  • Bisphenol A-Glycidyl Methacrylate / pharmacology
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Composite Resins / pharmacology*
  • Dental Materials / pharmacology*
  • Energy Metabolism / drug effects*
  • Glucose / metabolism
  • Glucosephosphate Dehydrogenase / drug effects
  • Glutathione / metabolism*
  • Glutathione Reductase / drug effects
  • HL-60 Cells
  • Humans
  • Lactic Acid / metabolism
  • Methacrylates / pharmacology*
  • Mitochondria / drug effects
  • Oxygen Consumption / drug effects
  • Polyethylene Glycols / pharmacology
  • Polymers
  • Polymethacrylic Acids / pharmacology

Substances

  • Composite Resins
  • Dental Materials
  • Methacrylates
  • Polymers
  • Polymethacrylic Acids
  • triethylene glycol dimethacrylate
  • Lactic Acid
  • Polyethylene Glycols
  • Bisphenol A-Glycidyl Methacrylate
  • hydroxyethyl methacrylate
  • Glucosephosphate Dehydrogenase
  • Glutathione Reductase
  • Glutathione
  • Glucose