Biotransformation of Food-Grade and Nanometric TiO<sub>2</sub> in the Oral–Gastro–Intestinal Tract: Driving Forces and Effect on the Toxicity toward Intestinal Epithelial Cells

<i>Background:</i> Oral exposure to titanium dioxide (TiO<sub>2</sub>) is common since it is widely used in food and pharmaceutical products. Concern on the safety of this substance has been recently raised, due to the presence of an ultrafine fraction in food-grade TiO<su...

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Main Authors: Arianna Marucco, Marion Prono, David Beal, Enrica Alasonati, Paola Fisicaro, Enrico Bergamaschi, Marie Carriere, Ivana Fenoglio
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Nanomaterials
Subjects:
Online Access:https://www.mdpi.com/2079-4991/10/11/2132
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author Arianna Marucco
Marion Prono
David Beal
Enrica Alasonati
Paola Fisicaro
Enrico Bergamaschi
Marie Carriere
Ivana Fenoglio
author_facet Arianna Marucco
Marion Prono
David Beal
Enrica Alasonati
Paola Fisicaro
Enrico Bergamaschi
Marie Carriere
Ivana Fenoglio
author_sort Arianna Marucco
collection DOAJ
description <i>Background:</i> Oral exposure to titanium dioxide (TiO<sub>2</sub>) is common since it is widely used in food and pharmaceutical products. Concern on the safety of this substance has been recently raised, due to the presence of an ultrafine fraction in food-grade TiO<sub>2</sub>. Discrepancy exists among data reported in in vitro and in vivo studies on intestinal acute/chronic toxicity of TiO<sub>2</sub>. This might be due to the different biological identity of TiO<sub>2</sub> in traditional in vitro test by respect in vivo conditions. <i>Methods:</i> One food-grade TiO<sub>2</sub> and two nanometric TiO<sub>2</sub> samples were treated with a simulated human digestive dystem (SHDS) in order to investigate the bio-transformation occurring to the particles once ingested in term of size distribution (Dynamic Light Scattering—DLS-, Flow Particle Imaging, Asymmetric Flow Field Flow Fractionation-AF4-) and surface modification (Electrophoretic Light Scattering—ELS-, Electron Paramagnetic Resonance Spectroscopy—EPR-). The effect of SHDS on the cyto-, genotoxicity and potential to induce oxidative stress towards human colorectal carcinoma HCT116 cells was also assessed. <i>Results:</i> Aggregation as a consequence of the high ionic strength of the gastric and intestinal simulated fluids was observed, together with the formation of a partially irreversible bio-corona containing phosphate ions and proteins. Such bio-corona led to a partial masking of the TiO<sub>2</sub> particles surface and reactivity. Pristine and treated TiO<sub>2</sub> nanoparticles showed comparable acute toxicity and genotoxicity toward HCT116 cells, whereas a small decrease of the induction of oxidative stress after treatment was observed. <i>Conclusions:</i> Overall the results underline the importance of SHDS as a tool to improve the predictive power of in vitro tests towards intestinal nanomaterial toxicity.
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spelling doaj.art-e10144526fdb4a1bba24bc94024a166e2023-11-20T18:39:31ZengMDPI AGNanomaterials2079-49912020-10-011011213210.3390/nano10112132Biotransformation of Food-Grade and Nanometric TiO<sub>2</sub> in the Oral–Gastro–Intestinal Tract: Driving Forces and Effect on the Toxicity toward Intestinal Epithelial CellsArianna Marucco0Marion Prono1David Beal2Enrica Alasonati3Paola Fisicaro4Enrico Bergamaschi5Marie Carriere6Ivana Fenoglio7Department of Chemistry, University of Torino, 10125 Torino, ItalyChimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST), University Grenoble Alpes, CEA, CNRS, IRIG, SyMMES, F-38000 Grenoble, FranceChimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST), University Grenoble Alpes, CEA, CNRS, IRIG, SyMMES, F-38000 Grenoble, FranceDépartement Biomédicale et Chimie Inorganique, Laboratoire National de Métrologie et D’essais, F-75724 Paris, FranceDépartement Biomédicale et Chimie Inorganique, Laboratoire National de Métrologie et D’essais, F-75724 Paris, FranceDepartment of Public Health and Pediatrics, University of Torino, 10126 Torino, ItalyChimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST), University Grenoble Alpes, CEA, CNRS, IRIG, SyMMES, F-38000 Grenoble, FranceDepartment of Chemistry, University of Torino, 10125 Torino, Italy<i>Background:</i> Oral exposure to titanium dioxide (TiO<sub>2</sub>) is common since it is widely used in food and pharmaceutical products. Concern on the safety of this substance has been recently raised, due to the presence of an ultrafine fraction in food-grade TiO<sub>2</sub>. Discrepancy exists among data reported in in vitro and in vivo studies on intestinal acute/chronic toxicity of TiO<sub>2</sub>. This might be due to the different biological identity of TiO<sub>2</sub> in traditional in vitro test by respect in vivo conditions. <i>Methods:</i> One food-grade TiO<sub>2</sub> and two nanometric TiO<sub>2</sub> samples were treated with a simulated human digestive dystem (SHDS) in order to investigate the bio-transformation occurring to the particles once ingested in term of size distribution (Dynamic Light Scattering—DLS-, Flow Particle Imaging, Asymmetric Flow Field Flow Fractionation-AF4-) and surface modification (Electrophoretic Light Scattering—ELS-, Electron Paramagnetic Resonance Spectroscopy—EPR-). The effect of SHDS on the cyto-, genotoxicity and potential to induce oxidative stress towards human colorectal carcinoma HCT116 cells was also assessed. <i>Results:</i> Aggregation as a consequence of the high ionic strength of the gastric and intestinal simulated fluids was observed, together with the formation of a partially irreversible bio-corona containing phosphate ions and proteins. Such bio-corona led to a partial masking of the TiO<sub>2</sub> particles surface and reactivity. Pristine and treated TiO<sub>2</sub> nanoparticles showed comparable acute toxicity and genotoxicity toward HCT116 cells, whereas a small decrease of the induction of oxidative stress after treatment was observed. <i>Conclusions:</i> Overall the results underline the importance of SHDS as a tool to improve the predictive power of in vitro tests towards intestinal nanomaterial toxicity.https://www.mdpi.com/2079-4991/10/11/2132foodTiO<sub>2</sub>intestinal cellssizesurfacebio-corona
spellingShingle Arianna Marucco
Marion Prono
David Beal
Enrica Alasonati
Paola Fisicaro
Enrico Bergamaschi
Marie Carriere
Ivana Fenoglio
Biotransformation of Food-Grade and Nanometric TiO<sub>2</sub> in the Oral–Gastro–Intestinal Tract: Driving Forces and Effect on the Toxicity toward Intestinal Epithelial Cells
Nanomaterials
food
TiO<sub>2</sub>
intestinal cells
size
surface
bio-corona
title Biotransformation of Food-Grade and Nanometric TiO<sub>2</sub> in the Oral–Gastro–Intestinal Tract: Driving Forces and Effect on the Toxicity toward Intestinal Epithelial Cells
title_full Biotransformation of Food-Grade and Nanometric TiO<sub>2</sub> in the Oral–Gastro–Intestinal Tract: Driving Forces and Effect on the Toxicity toward Intestinal Epithelial Cells
title_fullStr Biotransformation of Food-Grade and Nanometric TiO<sub>2</sub> in the Oral–Gastro–Intestinal Tract: Driving Forces and Effect on the Toxicity toward Intestinal Epithelial Cells
title_full_unstemmed Biotransformation of Food-Grade and Nanometric TiO<sub>2</sub> in the Oral–Gastro–Intestinal Tract: Driving Forces and Effect on the Toxicity toward Intestinal Epithelial Cells
title_short Biotransformation of Food-Grade and Nanometric TiO<sub>2</sub> in the Oral–Gastro–Intestinal Tract: Driving Forces and Effect on the Toxicity toward Intestinal Epithelial Cells
title_sort biotransformation of food grade and nanometric tio sub 2 sub in the oral gastro intestinal tract driving forces and effect on the toxicity toward intestinal epithelial cells
topic food
TiO<sub>2</sub>
intestinal cells
size
surface
bio-corona
url https://www.mdpi.com/2079-4991/10/11/2132
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