Human Intestinal Tissue Explant Exposure to Silver Nanoparticles Reveals Sex Dependent Alterations in Inflammatory Responses and Epithelial Cell Permeability

Abstract

Consumer products manufactured with antimicrobial silver nanoparticles (AgNPs) may affect the gastrointestinal (GI) system. The human GI-tract is complex and there are physiological and anatomical differences between human and animal models that limit comparisons between species. Thus, assessment of AgNP toxicity on the human GI-tract may require tools that allow for the examination of subtle changes in inflammatory markers and indicators of epithelial perturbation. Fresh tissues were excised from the GI-tract of human male and female subjects to evaluate the effects of AgNPs on the GI-system. The purpose of this study was to perform an assessment on the ability of the ex vivo model to evaluate changes in levels of pro-/anti-inflammatory cytokines/chemokines and mRNA expression of intestinal permeability related genes induced by AgNPs in ileal tissues. The ex vivo model preserved the structural and biological functions of the in-situ organ. Analysis of cytokine expression data indicated that intestinal tissue of male and female subjects responded differently to AgNP treatment, with male samples showing significantly elevated Granulocyte-macrophage colony-stimulating factor (GM-CSF) after treatment with 10 nm and 20 nm AgNPs for 2 h and significantly elevated RANTES after treatment with 20 nm AgNPs for 24 h. In contrast, tissues of female showed no significant effects of AgNP treatment at 2 h and significantly decreased RANTES (20 nm), TNF-α (10 nm), and IFN-γ (10 nm) at 24 h. Smaller size AgNPs (10 nm) perturbed more permeability-related genes in samples of male subjects, than in samples from female subjects. In contrast, exposure to 20 nm AgNPs resulted in upregulation of a greater number of genes in female-derived samples (36 genes) than in male-derived samples (8 genes). The ex vivo tissue model can distinguish sex dependent effects of AgNP and could serve as a translational non-animal model to assess the impacts of xenobiotics on human intestinal mucosa.

Food‐grade titanium dioxide decreases hematocrit and hemoglobin and increases compulsive‐like behavior in male mice

“…Additionally, evidence indicating that sex influences the toxicity induced by some nanomaterials or dietary emulsifiers is growing (Gokulan et al, 2020; Holder et al, 2019), which agrees with our results. Occasionally, the decrease in hematocrit is due to dehydration.…”

Ex Vivo Human Colon Tissue Exposure to Pristine Graphene Activates Genes Involved in the Binding, Adhesion and Proliferation of Epithelial Cells

“…Upon receipt, tissues were immediately transferred into a cocktail of 50% MACS tissue storage solution (Miltenyi Biotec, Bergisch Gladbach, Germany) and 50% RPMI-1640 (ATCC, Manassas, VA, USA) media containing 1% fetal bovine serum and 5% streptomycin/penicillin (ATCC; Manassas, VA, USA). Tissue biopsy punches 6.00 mm in size were collected and placed into the upper compartment of transwells (Corning Life Sciences, Union City, CA, USA) filled with 200 µL of growth media, as described previously [ 53 ]. The lower compartment of each transwell was filled with 1.0 mL of the same medium.…”

Dietary Nanoparticles Interact with Gluten Peptides and Alter the Intestinal Homeostasis Increasing the Risk of Celiac Disease

“…Interestingly, an increase was observed only after stimulations of the duodenal biopsies from CeD patients, but not from controls, suggesting that although mNPs could be innocuous for healthy subjects, they could be harmful for the celiac subjects. Although a recent paper by Gokulan et al [ 49 ] analyzes the effect of AgNPs on the human intestinal mucosa, it is quite difficult to compare their data with ours, due to differences in the time of the exposure as well as in the AgNPs concentration. However, even in their experimental conditions, no significant increase in IFN expression was observed after 2 h exposure in normal mucosa.…”