Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Apr;94(4):1191-1202.
doi: 10.1007/s00204-020-02694-6. Epub 2020 Mar 11.

Small silica nanoparticles transiently modulate the intestinal permeability by actin cytoskeleton disruption in both Caco-2 and Caco-2/HT29-MTX models

Raphaël Cornu  1 , Claire Chrétien  1 , Yann Pellequer  1 , Hélène Martin #  1 , Arnaud Béduneau #  2
Affiliations

Small silica nanoparticles transiently modulate the intestinal permeability by actin cytoskeleton disruption in both Caco-2 and Caco-2/HT29-MTX models

Raphaël Cornu et al. Arch Toxicol. 2020 Apr.

Abstract

Amorphous silica nanoparticles are widely used as pharmaceutical excipients and food additive (E551). Despite the potential human health risks of mineral nanoparticles, very few data regarding their oral toxicity are currently available. This study aims to evaluate and to understand the interactions of silica particles at 1 and 10 mg mL-1 with the intestinal barrier using a Caco-2 monolayer and a Caco-2/HT29-MTX co-culture. A size- and concentration-dependent reversible increase of the paracellular permeability is identified after a short-term exposure to silica nanoparticles. Nanoparticles of 30 nm induce the highest transepithelial electrical resistance drop whereas no effect is observed with 200 nm particles. Additive E551 affect the Caco-2 monolayer permeability. Mucus layer reduces the permeability modulation by limiting the cellular uptake of silica. After nanoparticle exposure, tight junction expression including Zonula occludens 1 (ZO-1) and Claudin 2 is not affected, whereas the actin cytoskeleton disruption of enterocytes and the widening of ZO-1 staining bands are observed. A complete permeability recovery is concomitant with the de novo filament actin assembly and the reduction of ZO-1 bands. These findings suggest the paracellular modulation by small silica particles is directly correlated to the alteration of the ZO-actin binding strongly involved in the stability of the tight junction network.

Keywords: Actin cytoskeleton; Caco-2 cells; Intestinal permeability; Silica nanoparticles; Tight junctions.

PubMed Disclaimer

References

    1. Athinarayanan J, Periasamy VS, Alsaif MA et al (2014) Presence of nanosilica (E551) in commercial food products: TNF-mediated oxidative stress and altered cell cycle progression in human lung fibroblast cells. Cell Biol Toxicol 30:89–100. https://doi.org/10.1007/s10565-014-9271-8 - DOI - PubMed
    1. Barahona F, Ojea-Jimenez I, Geiss O et al (2016) Multimethod approach for the detection and characterisation of food-grade synthetic amorphous silica nanoparticles. J Chromatogr A 1432:92–100. https://doi.org/10.1016/j.chroma.2015.12.058 - DOI - PubMed
    1. Billat P-A, Roger E, Faure S, Lagarce F (2017) Models for drug absorption from the small intestine: where are we and where are we going? Drug Discov Today 22:761–775. https://doi.org/10.1016/j.drudis.2017.01.007 - DOI - PubMed
    1. Brun E, Barreau F, Veronesi G et al (2014) Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in vitro gut epithelia. Part Fibre Toxicol 11:13. https://doi.org/10.1186/1743-8977-11-13 - DOI - PubMed - PMC
    1. Christen V, Camenzind M, Fent K (2014) Silica nanoparticles induce endoplasmic reticulum stress response, oxidative stress and activate the mitogen-activated protein kinase (MAPK) signaling pathway. Toxicol Rep 1:1143–1151. https://doi.org/10.1016/j.toxrep.2014.10.023 - DOI - PubMed - PMC

Publication types

Substances

LinkOut - more resources