title: Antioxidant combinations protect oral fibroblasts against metal-induced toxicity.
abstract: OBJECTIVE
  In dentistry, the use of metals in fillings, braces, implants, bridges and other prosthodontic restorations is a common practice. Previous studies revealed that zinc (Zn) and copper (Cu) released from gold alloys, and nickel (Ni) released from nickel-chromium alloys, have a highly cytotoxic effect on fibroblast cell cultures. Our working hypothesis is that oral fibroblasts are susceptible to damage from metals because they elevate reaction oxygen species (ROS). In this study, we investigated specific antioxidant (AO) combinations to determine if they counteract the effects of Cu, Ni and Zn on cultured oral fibroblast proliferation and oxidative damage.
  
  
  METHODS
  Oral fibroblasts were pretreated with Cu, Ni and Zn for 60min. Thereafter, cells were treated with 10(-5)M combinations of bioactive AO resveratrol (R), ferulic acid (F), phloretin (P) and tetrahydrocurcuminoids (T) (RFT, PFR, PFT) for 24h. Cell viability and DNA synthesis were monitored by 3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium (MTS) and 5-bromo-2-deoxyuridine (BrDU) assays. ROS was measured using the fluorescence response of dichlorodihydrofluorescein diacetate (DCF).
  
  
  RESULTS
  AO compounds increased recovery of cells exposed to Cu and Zn. Moreover, AO treatment induced DNA synthesis in the presence of the metal stressors. Cu and Ni stimulated production of ROS. PFR treatment decreased ROS in the presence of Cu, Ni and Zn.
  
  
  CONCLUSIONS
  These data indicate that pure AOs counteracted the detrimental effects of Cu, Ni, Zn on oral fibroblasts in vitro by increasing cell viability, and DNA synthesis and decreasing ROS activity.
authors: Departments of Biomedical Sciences, Texas A&M Health Science Center, Baylor College of Dentistry, Dallas, TX, United States. cpitn@yahoo.com
authors: Symone M
authors: SM
authors: San Miguel
authors: Lynne A
authors: LA
authors: Opperman
authors: Edward P
authors: EP
authors: Allen
authors: Jan E
authors: JE
authors: Zielinski
authors: Kathy K H
authors: KK
authors: Svoboda
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003300:Copper / Q000633:toxicity; D003373:Coumaric Acids / Q000008:administration & dosage / Q000627:therapeutic use; D003474:Curcumin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D003764:Dental Materials / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005347:Fibroblasts / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use; D005881:Gingiva / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008670:Metals / Q000633:toxicity*; D009532:Nickel / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D010513:Periodontal Ligament / Q000166:cytology / Q000187:drug effects*; D010636:Phenols / Q000008:administration & dosage / Q000627:therapeutic use; D010693:Phloretin / Q000008:administration & dosage / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D000077185:Resveratrol; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D013267:Stilbenes / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D015032:Zinc / Q000633:toxicity
chemical_list: D000975:Antioxidants; D003373:Coumaric Acids; D003764:Dental Materials; D004338:Drug Combinations; D016166:Free Radical Scavengers; D008670:Metals; D010636:Phenols; D017382:Reactive Oxygen Species; D013267:Stilbenes; C096277:tetrahydrocurcumin; D003300:Copper; D009532:Nickel; D004247:DNA; C004999:ferulic acid; D012264:Ribonucleotide Reductases; D003474:Curcumin; D015032:Zinc; D000077185:Resveratrol; D010693:Phloretin