Guo Zhongyuan, Martucci Nicole J, Moreno-Olivas Fabiola, Tako Elad, Mahler Gretchen J
Department of Biomedical Engineering, Binghamton University, Binghamton, NY, 13902.
Plant, Soil and Nutrition Laboratory, Agricultural Research Services, U.S. Department of Agriculture, Ithaca, NY.
NanoImpact. 2017 Jan;5:70-82. doi: 10.1016/j.impact.2017.01.002. Epub 2017 Jan 18.
Ingestion of titanium dioxide (TiO) 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 TiO nanoparticles with an cell culture model of the small intestinal epithelium, and to determine how acute or chronic exposure to nano-TiO influences intestinal barrier function, reactive oxygen species generation, proinflammatory signaling, nutrient absorption (iron, zinc, fatty acids), and brush border membrane enzyme function (intestinal alkaline phosphatase). A Caco-2/HT29-MTX cell culture model was exposed to physiologically relevant doses of TiO nanoparticles for acute (four hours) or chronic (five days) time periods. Exposure to TiO nanoparticles significantly decreased intestinal barrier function following chronic exposure. Reactive oxygen species (ROS) generation, proinflammatory signaling, and intestinal alkaline phosphatase activity all showed increases in response to nano-TiO. Iron, zinc, and fatty acid transport were significantly decreased following exposure to TiO nanoparticles. This is because nanoparticle exposure induced a decrease in absorptive microvilli in the intestinal epithelial cells. 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.
从农用化学品、加工食品和营养补充剂等产品中摄入二氧化钛（TiO）纳米颗粒几乎是不可避免的。胃肠道是人体与外部环境之间的关键界面，也是必需营养物质吸收的场所。本研究的目的是使用小肠上皮细胞培养模型来研究摄入30纳米二氧化钛纳米颗粒的影响，并确定急性或慢性暴露于纳米二氧化钛如何影响肠道屏障功能、活性氧生成、促炎信号传导、营养物质吸收（铁、锌、脂肪酸）以及刷状缘膜酶功能（肠碱性磷酸酶）。将Caco-2/HT29-MTX细胞培养模型暴露于生理相关剂量的二氧化钛纳米颗粒中，分别进行急性（四小时）或慢性（五天）暴露。慢性暴露于二氧化钛纳米颗粒后，肠道屏障功能显著下降。活性氧（ROS）生成、促炎信号传导和肠碱性磷酸酶活性均显示出对纳米二氧化钛的反应增加。暴露于二氧化钛纳米颗粒后，铁、锌和脂肪酸的转运显著减少。这是因为纳米颗粒暴露导致肠上皮细胞中吸收性微绒毛减少。营养转运蛋白基因表达也发生了改变，这表明细胞正在努力调节因摄入纳米颗粒而受到干扰的转运机制。总体而言，这些结果表明，生理相关剂量的纳米颗粒（通常从食物中摄入）暴露会在功能水平上影响肠上皮细胞。
