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Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in vitro gut epithelia.

ABSTRACT: BACKGROUND: TiO2 particles are commonly used as dietary supplements and may contain up to 36% of nano-sized particles (TiO2-NPs). Still impact and translocation of NPs through the gut epithelium is poorly documented. RESULTS: We show that, in vivo and ex vivo, agglomerates of TiO2-NPs cross both the regular ileum epithelium and the follicle-associated epithelium (FAE) and alter the paracellular permeability of the ileum and colon epithelia. In vitro, they accumulate in M-cells and mucus-secreting cells, much less in enterocytes. They do not cause overt cytotoxicity or apoptosis. They translocate through a model of FAE only, but induce tight junctions remodeling in the regular ileum epithelium, which is a sign of integrity alteration and suggests paracellular passage of NPs. Finally we prove that TiO2-NPs do not dissolve when sequestered up to 24 h in gut cells. CONCLUSIONS: Taken together these data prove that TiO2-NPs would possibly translocate through both the regular epithelium lining the ileum and through Peyer's patches, would induce epithelium impairment, and would persist in gut cells where they would possibly induce chronic damage.

SUBMITTER: Brun E

PROVIDER: S-EPMC3987106 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in vitro gut epithelia.

Brun Emilie E Barreau Frédérick F Veronesi Giulia G Fayard Barbara B Sorieul Stéphanie S Chanéac Corinne C Carapito Christine C Rabilloud Thierry T Mabondzo Aloïse A Herlin-Boime Nathalie N Carrière Marie M

Particle and fibre toxicology 20140325

<h4>Background</h4>TiO2 particles are commonly used as dietary supplements and may contain up to 36% of nano-sized particles (TiO2-NPs). Still impact and translocation of NPs through the gut epithelium is poorly documented.<h4>Results</h4>We show that, in vivo and ex vivo, agglomerates of TiO2-NPs cross both the regular ileum epithelium and the follicle-associated epithelium (FAE) and alter the paracellular permeability of the ileum and colon epithelia. In vitro, they accumulate in M-cells and m ...[more]

PMID: 24666995

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Project description:BackgroundThe terms agglomerates and aggregates are frequently used in the regulatory definition(s) of nanomaterials (NMs) and hence attract attention in view of their potential influence on health effects. However, the influence of nanoparticle (NP) agglomeration and aggregation on toxicity is poorly understood although it is strongly believed that smaller the size of the NPs greater the toxicity. A toxicologically relevant definition of NMs is therefore not yet available, which affects not only the risk assessment process but also hinders the regulation of nano-products. In this study, we assessed the influence of NP agglomeration on their toxicity/biological responses in vitro and in vivo.ResultsWe tested two TiO2 NPs with different primary sizes (17 and 117?nm) and prepared ad-hoc suspensions composed of small or large agglomerates with similar dispersion medium composition. For in vitro testing, human bronchial epithelial (HBE), colon epithelial (Caco2) and monocytic (THP-1) cell lines were exposed to these suspensions for 24?h and endpoints such as cytotoxicity, total glutathione, epithelial barrier integrity, inflammatory mediators and DNA damage were measured. Large agglomerates of 17?nm TiO2 induced stronger responses than small agglomerates for glutathione depletion, IL-8 and IL-1? increase, and DNA damage in THP-1, while no effect of agglomeration was observed with 117?nm TiO2. In vivo, C57BL/6JRj mice were exposed via oropharyngeal aspiration or oral gavage to TiO2 suspensions and, after 3?days, biological parameters including cytotoxicity, inflammatory cell recruitment, DNA damage and biopersistence were measured. Mainly, we observed that large agglomerates of 117?nm TiO2 induced higher pulmonary responses in aspirated mice and blood DNA damage in gavaged mice compared to small agglomerates.ConclusionAgglomeration of TiO2 NPs influences their toxicity/biological responses and, large agglomerates do not appear less active than small agglomerates. This study provides a deeper insight on the toxicological relevance of NP agglomerates and contributes to the establishment of a toxicologically relevant definition for NMs.

Project description:BackgroundGold nanoparticles (AuNPs) are promising candidates to design the next generation NP-based drug formulations specifically treating maternal, fetal or placental complications with reduced side effects. Profound knowledge on AuNP distribution and effects at the human placental barrier in dependence on the particle properties and surface modifications, however, is currently lacking. Moreover, the predictive value of human placental transfer models for NP translocation studies is not yet clearly understood, in particular with regards to differences between static and dynamic exposures. To understand if small (3-4 nm) AuNPs with different surface modifications (PEGylated versus carboxylated) are taken up and cross the human placental barrier, we performed translocation studies in a static human in vitro co-culture placenta model and the dynamic human ex vivo placental perfusion model. The samples were analysed using ICP-MS, laser ablation-ICP-MS and TEM analysis for sensitive, label-free detection of AuNPs.ResultsAfter 24 h of exposure, both AuNP types crossed the human placental barrier in vitro, although in low amounts. Even though cellular uptake was higher for carboxylated AuNPs, translocation was slightly increased for PEGylated AuNPs. After 6 h of perfusion, only PEGylated AuNPs were observed in the fetal circulation and tissue accumulation was similar for both AuNP types. While PEGylated AuNPs were highly stable in the biological media and provided consistent results among the two placenta models, carboxylated AuNPs agglomerated and adhered to the perfusion device, resulting in different cellular doses under static and dynamic exposure conditions.ConclusionsGold nanoparticles cross the human placental barrier in limited amounts and accumulate in placental tissue, depending on their size- and/or surface modification. However, it is challenging to identify the contribution of individual characteristics since they often affect colloidal particle stability, resulting in different biological interaction in particular under static versus dynamic conditions. This study highlights that human ex vivo and in vitro placenta models can provide valuable mechanistic insights on NP uptake and translocation if accounting for NP stability and non-specific interactions with the test system.

Dataset Information

Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in vitro gut epithelia.

Publications

Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in vitro gut epithelia.

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