Biodistribution and intestinal inflammatory response following voluntary oral intake of silver nanoparticles by C57BL/6J mice

Abstract

Silver nanoparticles (AgNP) are among the most widely commercialized nanomaterials globally, with applications in medicine and the food industry. Consequently, the increased use of AgNP in the food industry has led to an unavoidable rise in human exposure to these nanoparticles. Their widespread use raises concerns about potential hazards to human health, specifically their intestinal pro-inflammatory effects. Thus, the main objective of this study was to evaluate the biological effects of two subacute doses of 5 nm polyvinylpyrrolidone (PVP)-AgNP in C57BL/6J mice. One mg/kg body weight or 10 mg/kg bw was provided once a day for 14 days, using a new technology (HaPILLness) that allows voluntary, stress-free, and accurate oral dosing. It was observed that after oral ingestion, while AgNP is biodistributed throughout the entire organism, most of the ingested dose is excreted in the feces. The passage and accumulation of AgNP throughout the intestine instigated a prominent inflammatory response, marked by significant histological, vascular, and cellular transformations. This response was driven by the activation of the nuclear factor-кB (NF-кB) inflammatory pathway, ultimately leading to the generation of multiple cytokines and chemokines.

In Vivo Pro-Inflammatory Effects of Silver Nanoparticles on the Colon Depend on Time and Route of Exposure

“…Levels of IL-6, IL-12, TNF-α and IL-10 increased across the experimental period and were elevated in both time points. Similar results were described by Sousa et al [44] following 14 days of oral AgNP administration (1 or 10 mg/kg bw) to mice. They observed increased levels of TNF-α and IL-10 in the colon in both doses, as well as an increase in IL-6 and IL-12 treated with the lower, but not the higher dose.…”

Metabolomics Analysis for Unveiling the Toxicological Mechanism of Silver Nanoparticles Using an In Vitro Gastrointestinal Digestion Model

“…Numerous animal studies have demonstrated that AgNPs could be found in the intestine after being orally ingested, − and the chronic oral exposure to AgNPs damaged the epithelial cell microvilli and increased numbers of goblet cells in the intestine, suggesting that AgNPs may disorder the intestinal immune microenvironment. − The accumulation of AgNPs in the intestine can causes inflammation, through damaging the epithelial barrier and activating immune cells. This leads to their infiltration in the intestinal lining, the activation of transcription factors like nuclear factor kappa B (NF-κB), and the release of inflammatory substances such as cytokines and chemokines. , Recent studies reported that the oral exposure of AgNPs can also induce disturbances in the gut microbiota. , Ultimately, these events will contribute to the development or worsening of various gut diseases, such as inflammatory bowel diseases (IBDs, such as Crohn’s disease and ulcerative colitis). − Although the toxic effects of AgNPs in the gastrointestinal tract (GIT) have been confirmed, the gastrointestinal fate of AgNPs, including transformation and subsequent cellular interactions, remains not well understood, which is of key importance to assess their health risks. − Consequently, an in vitro digestive simulation is necessary to specifically explore the correlation between the transformation and toxicity of AgNPs during gastrointestinal digestion.…”