title: Pharmacological and toxicological effects of co-exposure of human gingival fibroblasts to silver nanoparticles and sodium fluoride.
abstract: BACKGROUND
  Silver nanoparticles (AgNPs) and fluoride (F) are pharmacological agents widely used in oral medicine and dental practice due to their anti-microbial/anti-cavity properties. However, risks associated with the co-exposure of local cells and tissues to these xenobiotics are not clear. Therefore, we have evaluated the effects of AgNPs and F co-exposure on human gingival fibroblast cells.
  
  
  METHODS
  Human gingival fibroblast cells (CRL-2014) were exposed to AgNPs and/or F at different concentrations for up to 24 hours. Cellular uptake of AgNPs was examined by transmission electron microscopy. Downstream inflammatory effects and oxidative stress were measured by real-time quantitative polymerase chain reaction (PCR) and reactive oxygen species (ROS) generation. Cytotoxicity and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and real-time quantitative PCR and flow cytometry, respectively. Finally, the involvement of mitogen-activated protein kinases (MAPK) was studied using Western blot.
  
  
  RESULTS
  We found that AgNPs penetrated the cell membrane and localized inside the mitochondria. Co-incubation experiments resulted in increased oxidative stress, inflammation, and apoptosis. In addition, we found that co-exposure to both xenobiotics phosphorylated MAPK, particularly p42/44 MAPK.
  
  
  CONCLUSIONS
  A combined exposure of human fibroblasts to AgNPs and F results in increased cellular damage. Further studies are needed in order to evaluate pharmacological and potentially toxicological effects of AgNPs and F on oral health.
authors.affiliation: Department of Medicinal Chemistry, Medical University Gdansk, Debinki, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Inkielewicz-Stepniak
authors.affiliation: The School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland ; School of Medicine, Trinity College Dublin, Dublin, Ireland ; Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Santos-Martinez
authors.affiliation: The School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland ; Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland.
authors.forename: Carlos
authors.initials: C
authors.lastname: Medina
authors.affiliation: The School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland ; Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland.
authors.forename: Marek W
authors.initials: MW
authors.lastname: Radomski
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004338:Drug Combinations; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology*; D005881:Gingiva / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D053768:Metal Nanoparticles / Q000633:toxicity*; D012834:Silver / Q000633:toxicity*; D012969:Sodium Fluoride / Q000633:toxicity*
chemical_list: D004338:Drug Combinations; D012834:Silver; D012969:Sodium Fluoride
keywords: apoptosis; inflammation; matrix; metalloproteinases; mitogen-activated protein kinases; nanoparticles; oxidative stress
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