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

Brun E, Barreau F, Veronesi G, Fayard B, Sorieul S, Chanéac C, Carapito C, Rabilloud T, Mabondzo A, Herlin-Boime N, Carrière M - Part Fibre Toxicol (2014)

Bottom Line: 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.Finally we prove that TiO2-NPs do not dissolve when sequestered up to 24 h in gut cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Université Grenoble Alpes, INAC, SCIB, F-38000, Grenoble, France 14 CEA, INAC, SCIB, F-38054 Grenoble, France. marie.carriere@cea.fr.

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.

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Related in: MedlinePlus

Particle-induced X-ray emission (PIXE) spectra and maps of P and Ti distribution. PIXE spectra displaying the regions of interest (between dashed lines) selected for mapping and quantification of P and Ti content, on Caco-2 monoculture (A) and Caco-2/HT29-MTX co-culture (B). Chemical element distribution in the Caco-2 monoculture (C-E), Caco-2/HT29-MTX co-culture (F-H) and the Caco-2/RajiB co-culture (I-K), exposed to 50 μg/mL TiO2-NPs for 24 h: distribution of phosphorous (P) (C, F, I) and of titanium (Ti) (D, G, J), merge of P and Ti distribution maps (E, H, K).
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Figure 4: Particle-induced X-ray emission (PIXE) spectra and maps of P and Ti distribution. PIXE spectra displaying the regions of interest (between dashed lines) selected for mapping and quantification of P and Ti content, on Caco-2 monoculture (A) and Caco-2/HT29-MTX co-culture (B). Chemical element distribution in the Caco-2 monoculture (C-E), Caco-2/HT29-MTX co-culture (F-H) and the Caco-2/RajiB co-culture (I-K), exposed to 50 μg/mL TiO2-NPs for 24 h: distribution of phosphorous (P) (C, F, I) and of titanium (Ti) (D, G, J), merge of P and Ti distribution maps (E, H, K).

Mentions: We then evaluated TiO2-NP accumulation in the three in vitro models, by using μPIXE. TiO2-NP accumulation in Caco-2 monocultures was very low: PIXE spectra recorded on this model showed no clear Ti line (Figure 4A). Conversely the PIXE spectra recorded on the Caco-2/HT29-MTX co-culture showed two intense Ti lines, corresponding to the Ti-Kα and -Kβ emissions (Figure 4B). Images of Ti distribution logically showed very few Ti-rich areas in the Caco-2 monoculture (Figure 4C-E), while Ti-rich areas were observed in the Caco-2/HT29-MTX co-culture (Figure 4F-H, arrows). Ti accumulation was also significant in the Caco-2/RajiB coculture (Figure 4I-K). It suggests that the presence of HT29-MTX cells throughout Caco-2 monolayer, as well as partial differentiation of Caco-2 cells into M-cells allowed TiO2-NPs to be accumulated in cells. Ti distribution images were also recorded on cell cross-sections (Additional file 5), proving that the Ti-rich areas were really inside the cells, and not deposited on their surface.


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

Brun E, Barreau F, Veronesi G, Fayard B, Sorieul S, Chanéac C, Carapito C, Rabilloud T, Mabondzo A, Herlin-Boime N, Carrière M - Part Fibre Toxicol (2014)

Particle-induced X-ray emission (PIXE) spectra and maps of P and Ti distribution. PIXE spectra displaying the regions of interest (between dashed lines) selected for mapping and quantification of P and Ti content, on Caco-2 monoculture (A) and Caco-2/HT29-MTX co-culture (B). Chemical element distribution in the Caco-2 monoculture (C-E), Caco-2/HT29-MTX co-culture (F-H) and the Caco-2/RajiB co-culture (I-K), exposed to 50 μg/mL TiO2-NPs for 24 h: distribution of phosphorous (P) (C, F, I) and of titanium (Ti) (D, G, J), merge of P and Ti distribution maps (E, H, K).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3987106&req=5

Figure 4: Particle-induced X-ray emission (PIXE) spectra and maps of P and Ti distribution. PIXE spectra displaying the regions of interest (between dashed lines) selected for mapping and quantification of P and Ti content, on Caco-2 monoculture (A) and Caco-2/HT29-MTX co-culture (B). Chemical element distribution in the Caco-2 monoculture (C-E), Caco-2/HT29-MTX co-culture (F-H) and the Caco-2/RajiB co-culture (I-K), exposed to 50 μg/mL TiO2-NPs for 24 h: distribution of phosphorous (P) (C, F, I) and of titanium (Ti) (D, G, J), merge of P and Ti distribution maps (E, H, K).
Mentions: We then evaluated TiO2-NP accumulation in the three in vitro models, by using μPIXE. TiO2-NP accumulation in Caco-2 monocultures was very low: PIXE spectra recorded on this model showed no clear Ti line (Figure 4A). Conversely the PIXE spectra recorded on the Caco-2/HT29-MTX co-culture showed two intense Ti lines, corresponding to the Ti-Kα and -Kβ emissions (Figure 4B). Images of Ti distribution logically showed very few Ti-rich areas in the Caco-2 monoculture (Figure 4C-E), while Ti-rich areas were observed in the Caco-2/HT29-MTX co-culture (Figure 4F-H, arrows). Ti accumulation was also significant in the Caco-2/RajiB coculture (Figure 4I-K). It suggests that the presence of HT29-MTX cells throughout Caco-2 monolayer, as well as partial differentiation of Caco-2 cells into M-cells allowed TiO2-NPs to be accumulated in cells. Ti distribution images were also recorded on cell cross-sections (Additional file 5), proving that the Ti-rich areas were really inside the cells, and not deposited on their surface.

Bottom Line: 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.Finally we prove that TiO2-NPs do not dissolve when sequestered up to 24 h in gut cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Université Grenoble Alpes, INAC, SCIB, F-38000, Grenoble, France 14 CEA, INAC, SCIB, F-38054 Grenoble, France. marie.carriere@cea.fr.

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.

Show MeSH
Related in: MedlinePlus