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Use of Physiologically-Based In Vitro Models of the Gastrointestinal Tract to Study SiO2 and TiO2 Nanoparticle Interactions with Nutrient Absorptio

Posted on:2018-04-29Degree:Ph.DType:Dissertation
University:State University of New York at BinghamtonCandidate:Guo, ZhongyuanFull Text:PDF
GTID:1471390020957610Subject:Biomedical engineering
Abstract/Summary:
Ingestion of silicon dioxide (SiO2) and titanium dioxide (TiO2) nanoparticles from products such as agricultural chemicals, processed food, and nutritional supplements is nearly unavoidable. The gastrointestinal tract serves as a critical interface between the body and the external environment, and is the site of essential nutrient absorption. The goal of this study was to examine the effects of ingesting the 30 nm SiO2 and TiO2 nanoparticles with an in vitro cell culture model of the small intestinal epithelium, and to determine how acute or chronic exposure to nano-TiO2 affects intestinal barrier function, reactive oxygen species generation, pro-inflammatory signaling, and nutrient absorption (iron, zinc, glucose, and lipids). SiO2 and TiO2 NPs with a primary size of 30 nm are spherical and agglomerate in water and medium. The digested SiO2 and TiO2 NPs with naturalistically simulated gastric fluid dispersant failed to affect lipid uptake significantly, but glucose transport and uptake were blocked by digested SiO2/TiO2 NPs or by simulated gastric fluid dispersant. A Caco-2/HT29-MTX cell culture model was exposed to physiologically relevant doses of TiO2 nanoparticles for acute (four hours) or chronic (five days) time periods. Exposure to TiO2 nanoparticles significantly decreased intestinal barrier function following chronic exposure. Reactive oxygen species (ROS) generation and pro-inflammatory signaling showed increases in response to nano-SiO2 and nano-TiO2. Iron and zinc were significantly decreased following both acute and chronic exposure to SiO2 and TiO2 nanoparticles. This is likely because nanoparticle exposure induced a decrease in absorptive microvilli in the intestinal epithelial cells, but the damage to microvilli caused by TiO2 was remediated by beneficial bacteria. Nutrient transporter protein gene expression was also altered, suggesting that cells are working to regulate the transport mechanisms disturbed by nanoparticle ingestion. Overall, these results show that intestinal epithelial cells are affected at a functional level by physiologically relevant exposure to nanoparticles commonly ingested from food.
Keywords/Search Tags:Tio2, Sio2, Nanoparticle, Intestinal, Exposure, Nutrient
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