Oxidative stress-mediated inhibition of intestinal epithelial cell proliferation by silver nanoparticles

- Silver nanoparticles induced cytotoxicity, oxidative stress, cell cycle arrest.
- Silver nanoparticles inhibited cell proliferation.
- In vitro digestion of silver nanoparticles altered the adsorbed surface species.
- No inhibition of cell proliferation was observed in confluent cells.

Given the increasing use of silver nanoparticles (Ag NP) by the food and food packaging industries, this study investigated potential consequences of Ag NP ingestion in intestinal epithelial C2BBe1 cells. Treatment of proliferating cells (<10,000 cells/cm2) with 0.25 μg/cm2 (1.25 μg/mL) of 23 nm Ag NP for 24 h induced 15% necrotic cell death and an 80% reduction in metabolic activity and decreased the GSH/GSSG ratio, indicating oxidative stress. G2/M phase cell cycle arrest and complete inhibition of cell proliferation was also induced by Ag NP treatment. Simulated in vitro digestion of Ag NP prior to cell exposure required the use of slightly higher doses to induce the same toxicity, likely due to slower Ag dissolution. Treatment of cells with silica, titania, and ZnO NP partially inhibited cell proliferation, but inhibition at low doses was unique to Ag NP. These data suggest that Ag NP induces oxidative stress, cell cycle arrest, and the inhibition of cell proliferation. However, toxicity and induction of oxidative stress were not observed in confluent cells (>100,000 cells/cm2) treated with 10 μg/cm2 (40-50 μg/mL) Ag NP, indicating that these cells are less sensitive to Ag NP.