title: Alterations of energy metabolism and glutathione levels of HL-60 cells induced by methacrylates present in composite resins.
abstract: OBJECTIVE
  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.
authors.affiliation: Biochemistry and Clinical Biochemistry Institute, School of Medicine, Catholic University, Rome, Italy. g.nocca@rm.unicatt.it
authors.forename: G
authors.initials: G
authors.lastname: Nocca
authors.forename: F
authors.initials: F
authors.lastname: De Palma
authors.forename: A
authors.initials: A
authors.lastname: Minucci
authors.forename: P
authors.initials: P
authors.lastname: De Sole
authors.forename: G E
authors.initials: GE
authors.lastname: Martorana
authors.forename: C
authors.initials: C
authors.lastname: Callà
authors.forename: C
authors.initials: C
authors.lastname: Morlacchi
authors.forename: M L
authors.initials: ML
authors.lastname: Gozzo
authors.forename: G
authors.initials: G
authors.lastname: Gambarini
authors.forename: C
authors.initials: C
authors.lastname: Chimenti
authors.forename: B
authors.initials: B
authors.lastname: Giardina
authors.forename: A
authors.initials: A
authors.lastname: Lupi
mesh_terms: D017438:Bisphenol A-Glycidyl Methacrylate / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003188:Composite Resins / Q000494:pharmacology*; D003764:Dental Materials / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008689:Methacrylates / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011092:Polyethylene Glycols / Q000494:pharmacology; D011108:Polymers; D011109:Polymethacrylic Acids / Q000494:pharmacology
chemical_list: D003188:Composite Resins; D003764:Dental Materials; D008689:Methacrylates; D011108:Polymers; D011109:Polymethacrylic Acids; C020946:triethylene glycol dimethacrylate; D019344:Lactic Acid; D011092:Polyethylene Glycols; D017438:Bisphenol A-Glycidyl Methacrylate; C005044:hydroxyethyl methacrylate; D005954:Glucosephosphate Dehydrogenase; D005980:Glutathione Reductase; D005978:Glutathione; D005947:Glucose