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Title: Evaluation of the cytotoxic and cellular proteome impacts of food-grade TiO2 (E171) using simulated gastrointestinal digestions and a tri-culture small intestinal epithelial model

Abstract

Engineered nanomaterials (ENMs) are widely used in the food industry; however, regulations for ENMs in food are still in the early stages of development due to insufficient health data. This study investigated the cytotoxicity and changes to the proteomic profile in an in vitro small intestinal epithelium model after exposure to digested food models containing the ubiquitous engineered particulate food additive, TiO2 (E171). TiO2 at 0.75% or 1.5% (w/w) concentrations in either a fasting food model (FFM) or a standardized food model (SFM) based on American diet were digested using an in vitro oral-gastric-small intestinal simulator, and the resulting digestas were applied to a small intestinal epithelium tri-culture cellular model. Effects on cell layer integrity, cytotoxicity, and oxidative stress were assessed. In order to explore impact on cellular processes beyond basic cytotoxicity, mass spectrometrybased quantitative proteomic analyses of control and exposed tri-culture cells was performed. TiO2 in FFM, but not in SFM, produced significant, dose-dependent cytotoxicity, and at the higher dose caused significant oxidative stress, indicative of a food matrix effect. No significant perturbations of the cellular proteome were observed with TiO2 in either FFM or SFM food models. However, proteins involved in the tricarboxylic acid (TCA) cycle, gluconeogenesis, andmore » translation were up-regulated by digestas from SFM compared to those from FFM, also indicative of food matrix effects in the case of food models alone. Interestingly, the differences in profiles between the two food models was more pronounced in the presence of TiO2 indicative of food matrix effects. Together, these results indicate that TiO2 in a fasting diet may be slightly cytotoxic, and that ingested TiO2 does not significantly alter the epithelial proteome, whereas the food matrix alone can have a dramatic effect on the proteome.« less

Authors:
 [1];  [2];  [1];  [2];  [2];  [2]; ORCiD logo [2];  [1]
  1. Harvard University
  2. BATTELLE (PACIFIC NW LAB)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1580588
Report Number(s):
PNNL-SA-147195
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
NanoImpact
Additional Journal Information:
Journal Volume: 17
Country of Publication:
United States
Language:
English

Citation Formats

Cao, Xiaoqiong, Zhang, Tong, DeLoid, Glen M., Gaffrey, Matthew J., Weitz, Karl K., Thrall, Brian D., Qian, Weijun, and Demonkritou, Philip. Evaluation of the cytotoxic and cellular proteome impacts of food-grade TiO2 (E171) using simulated gastrointestinal digestions and a tri-culture small intestinal epithelial model. United States: N. p., 2020. Web. doi:10.1016/j.impact.2019.100202.
Cao, Xiaoqiong, Zhang, Tong, DeLoid, Glen M., Gaffrey, Matthew J., Weitz, Karl K., Thrall, Brian D., Qian, Weijun, & Demonkritou, Philip. Evaluation of the cytotoxic and cellular proteome impacts of food-grade TiO2 (E171) using simulated gastrointestinal digestions and a tri-culture small intestinal epithelial model. United States. doi:10.1016/j.impact.2019.100202.
Cao, Xiaoqiong, Zhang, Tong, DeLoid, Glen M., Gaffrey, Matthew J., Weitz, Karl K., Thrall, Brian D., Qian, Weijun, and Demonkritou, Philip. Thu . "Evaluation of the cytotoxic and cellular proteome impacts of food-grade TiO2 (E171) using simulated gastrointestinal digestions and a tri-culture small intestinal epithelial model". United States. doi:10.1016/j.impact.2019.100202.
@article{osti_1580588,
title = {Evaluation of the cytotoxic and cellular proteome impacts of food-grade TiO2 (E171) using simulated gastrointestinal digestions and a tri-culture small intestinal epithelial model},
author = {Cao, Xiaoqiong and Zhang, Tong and DeLoid, Glen M. and Gaffrey, Matthew J. and Weitz, Karl K. and Thrall, Brian D. and Qian, Weijun and Demonkritou, Philip},
abstractNote = {Engineered nanomaterials (ENMs) are widely used in the food industry; however, regulations for ENMs in food are still in the early stages of development due to insufficient health data. This study investigated the cytotoxicity and changes to the proteomic profile in an in vitro small intestinal epithelium model after exposure to digested food models containing the ubiquitous engineered particulate food additive, TiO2 (E171). TiO2 at 0.75% or 1.5% (w/w) concentrations in either a fasting food model (FFM) or a standardized food model (SFM) based on American diet were digested using an in vitro oral-gastric-small intestinal simulator, and the resulting digestas were applied to a small intestinal epithelium tri-culture cellular model. Effects on cell layer integrity, cytotoxicity, and oxidative stress were assessed. In order to explore impact on cellular processes beyond basic cytotoxicity, mass spectrometrybased quantitative proteomic analyses of control and exposed tri-culture cells was performed. TiO2 in FFM, but not in SFM, produced significant, dose-dependent cytotoxicity, and at the higher dose caused significant oxidative stress, indicative of a food matrix effect. No significant perturbations of the cellular proteome were observed with TiO2 in either FFM or SFM food models. However, proteins involved in the tricarboxylic acid (TCA) cycle, gluconeogenesis, and translation were up-regulated by digestas from SFM compared to those from FFM, also indicative of food matrix effects in the case of food models alone. Interestingly, the differences in profiles between the two food models was more pronounced in the presence of TiO2 indicative of food matrix effects. Together, these results indicate that TiO2 in a fasting diet may be slightly cytotoxic, and that ingested TiO2 does not significantly alter the epithelial proteome, whereas the food matrix alone can have a dramatic effect on the proteome.},
doi = {10.1016/j.impact.2019.100202},
journal = {NanoImpact},
number = ,
volume = 17,
place = {United States},
year = {2020},
month = {1}
}