Tuning the inflammatory response to silver nanoparticles via quercetin in Caco-2 (co-)cultures as model of the human intestinal mucosa

Toxicol Lett. 2016 Jun 24:253:36-45. doi: 10.1016/j.toxlet.2016.04.018. Epub 2016 Apr 22.

Abstract

Interaction of nanoparticles with food matrix components may cause unpredictable health complications. Using an improved Caco-2 cell-based in vitro (co-)culture model the potential of quercetin as one of the major food flavonoids to alter the effect of silver nanoparticles (Ag-NPs) <20 nm in the human intestinal mucosa at real life concentrations was investigated. Ag-NPs (15-90 μg/ml) decreased cell viability and reduced thiol groups, induced oxidative/nitrosative stress and lipid peroxidation and led to activity changes of various antioxidant enzymes after 3h exposure. The contribution of Ag(+) ions within the concentrations released from nanoparticles was shown to be less important, compared to Ag-NPs. While leading to inflammatory response in the intestines, Ag-NPs, paradoxically, also showed a potential anti-infammatory effect manifested in down-regulated IL-8 levels. Quercetin, co-administered with Ag-NPs, led to a reduction of cytotoxicity, oxidative stress, and recovered metabolic activity of Caco-2 cells, suggesting the protective effects of this flavonoid against the harmful effect of Ag-NPs. Quercetin not only alleviated the effect of Ag-NPs on the gastrointestinal cells, but also demonstrated a potential to serve as a tool for reversible modulation of intestinal permeability.

Keywords: Gastrointestinal tract; Inflammatory response; Oxidative and nitrosative stress; Quercetin; Silver nanoparticles.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Caco-2 Cells
  • Cell Survival / drug effects
  • Coculture Techniques
  • Cytoprotection
  • Dose-Response Relationship, Drug
  • Humans
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Lipid Peroxidation / drug effects
  • Metal Nanoparticles*
  • Oxidative Stress / drug effects
  • Quercetin / pharmacology*
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism
  • Risk Assessment
  • Silver Compounds / toxicity*

Substances

  • Anti-Inflammatory Agents
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Silver Compounds
  • Quercetin