Silicon dioxide nanoparticle exposure affects small intestine function in an in vitro model

• Published in: Nanotoxicology 2018-06, Vol.12 (5), p.485-508
• Main Authors: Guo, Zhongyuan, Martucci, Nicole J., Liu, Yizhong, Yoo, Eusoo, Tako, Elad, Mahler, Gretchen J.
• Format: Article
• Language: English
• Subjects: Absorption; Absorptivity; Alkaline phosphatase; Caco-2 Cells; Chronic exposure; Coculture Techniques; Consumer products; Drug delivery; Drug delivery systems; Epithelium; Exposure; Food; Food packaging; Gene expression; Goblet cells; HT29 Cells; Humans; IAP protein; Inflammation; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestine, Small - drug effects; Intestine, Small - physiology; Iron; Nanomaterials; Nanoparticles; Nanoparticles - toxicity; Nanotechnology; Nutrient availability; Nutrient transport; Nutrients; Oral administration; Oxidative stress; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; risk assessment; Silicon; Silicon dioxide; Silicon Dioxide - toxicity; SiO; Small intestine; Zinc
• ISSN: 1743-5390; 1743-5404
• DOI: 10.1080/17435390.2018.1463407

The use of nanomaterials to enhance properties of food and improve delivery of orally administered drugs has become common, but the potential health effects of these ingested nanomaterials remain unknown. The goal of this study is to characterize the properties of silicon dioxide (SiO 2 ) nanoparticles (NP) that are commonly used in food and food packaging, and to investigate the effects of physiologically realistic doses of SiO 2 NP on gastrointestinal (GI) health and function. In this work, an in vitro model composed of Caco-2 and HT29-MTX co-cultures, which represent absorptive and goblet cells, was used. The model was exposed to well-characterized SiO 2 NP for acute (4 h) and chronic (5 d) time periods. SiO 2 NP exposure significantly affected iron (Fe), zinc (Zn), glucose, and lipid nutrient absorption. Brush border membrane intestinal alkaline phosphatase (IAP) activity was increased in response to nano-SiO 2 . The barrier function of the intestinal epithelium, as measured by transepithelial electrical resistance, was significantly decreased in response to chronic exposure. Gene expression and oxidative stress formation analysis showed NP altered the expression levels of nutrient transport proteins, generated reactive oxygen species, and initiated pro-inflammatory signaling. SiO 2 NP exposure damaged the brush border membrane by decreasing the number of intestinal microvilli, which decreased the surface area available for nutrient absorption. SiO 2 NP exposure at physiologically relevant doses ultimately caused adverse outcomes in an in vitro model.