title: Size and dose dependent effects of silver nanoparticle exposure on intestinal permeability in an in vitro model of the human gut epithelium.
abstract: BACKGROUND
  The antimicrobial activity of silver nanoparticles (AgNP) has led to interest in their use in consumer products such as food contact materials, utensils, and storage containers. Incorporation of these materials into items intended for food processing and storage suggests that consumer use of these products could result in gastrointestinal exposure to AgNP, should the nanoparticles migrate from the product. The health impact of AgNP exposure is unknown, especially effects related to intestinal epithelial permeability and barrier function. This study examined the effects of AgNP exposure of different sizes (10, 20, 75 and 110 nm) and doses (20 and 100 µg/mL) on the permeability of T84 human colonic epithelial cells, which serve as an in vitro model of the human gut epithelium.
  
  
  RESULTS
  Results showed that effects of AgNP on the T84 epithelial cells were size- and dose-dependent, with the 10 nm AgNP causing the most significant changes. Changes in permeability of the epithelial cell monolayer, as measured by transepithelial electrical resistance, after exposure to 10 nm AgNP were most dramatic at the highest dose (100 µg/mL), but also observed at the lower dose (20 µg/mL). AgNP could be visualized inside cells using transmission electron microscopy and silver was detected in basal wells using inductively coupled plasma-mass spectrometry. Exposure to AgNP significantly affected the expression of genes involved in anchoring tight junctions, cellular proliferation and signaling, endocytosis, and cell-cell adhesion, with the 10 nm AgNP having the greatest effect.
  
  
  CONCLUSIONS
  The results of this study show that small-size AgNP have significant effects on intestinal permeability in an in vitro model of the human gastrointestinal epithelium. Such effects have the potential to compromise the integrity of the intestinal epithelium and this disruption of barrier function could have health consequences for the gastrointestinal tract.
authors.affiliation: Division of Microbiology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR, 72079, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Williams
authors.affiliation: Division of Microbiology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR, 72079, USA.
authors.forename: Kuppan
authors.initials: K
authors.lastname: Gokulan
authors.affiliation: Division of Microbiology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR, 72079, USA.
authors.forename: Carl E
authors.initials: CE
authors.lastname: Cerniglia
authors.affiliation: Division of Microbiology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR, 72079, USA. sangeeta.khare@fda.hhs.gov.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Khare
mesh_terms: D002460:Cell Line; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry*; D008954:Models, Biological; D010316:Particle Size; D012834:Silver / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D012834:Silver
keywords: Barrier function; Cell junctions; Intestinal permeability; Silver nanoparticles