Titanium dioxide nanoparticle ingestion alters nutrient absorption in an in vitro model of the small intestine

Abstract

Ingestion of 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 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 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 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, proinflammatory signaling, and intestinal alkaline phosphatase activity all showed increases in response to nano-TiO2. Iron, zinc, and fatty acid transport were significantly decreased following exposure to TiO2 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.

Simultaneous Quantification and Visualization of Titanium Dioxide Nanomaterial Uptake at the Single Cell Level in an In Vitro Model of the Human Small Intestine

“…It was shown that titanium dioxide NMs with a diameter of 30 nm led to an decreased iron and zinc transport in cells . It was suggested that the transport mechanisms were disturbed by TiO 2 NM ingestion . This goes along with our findings, where decreased zinc and iron cellular concentrations were observed, even under nontoxic exposure conditions .…”

<p>NLRP3 inflammasome, oxidative stress, and apoptosis induced in the intestine and liver of rats treated with titanium dioxide nanoparticles: in vivo and in vitro study</p>

“…36 Meena et al 15 reported Based on the results from in vitro and in vivo experiments, it was found that TiO 2 NP could cause oxidative stress, inflammation, apoptosis, and pathological changes in organs such as the intestine and the liver. 4,38,39 In the present experiment, TiO 2 NP induced toxicity, apoptosis, and increased ROS levels in HepG2 and Caco-2 cells. HepG2 cells are an appropriate in vitro model for the study of polarized human hepatocytes, as they secrete various key proteins that are vital for the study of cytotoxicity induced by NPs.…”

“…[1][2][3] Titanium dioxide nanoparticles (TiO 2 NPs) are widely used in industries such as paper and also in plastics, paints, ceramics, cosmetics, water/air purifiers, agricultural chemicals, toothpastes, and sunscreens. 3,4 They are also used in the food industry as whiteners in sauces and creamers. 5 Due to the high use of this compound, the question arises whether TiO 2 NPs can cause harm to basic tissues such as the intestine (the site of NP absorption) and the liver (the site of NP metabolism and detoxification).…”

“…9 Engineered TiO 2 NPs have become a commonly ingested material, and the influences of NPs on intestinal health function and structure are not well-recognized. 4 On the other hand, the liver is a multicellular organ that plays a role in the activation and elimination of many metabolites. 20 Studies have shown that the liver is the most important site for NP accumulation, which may be induced directly from intentional ingestion or indirectly through many food containers or secondary ingestion of inhaled NPs.…”

Encapsulation of colorants by natural polymers for food applications

“…The most well-known and widely used colorant is titanium dioxide, which accounts for 70% of the total production volume of pigments worldwide [6]. However, additional research on this topic is necessary to provide a good overview of the potential long-term negative effects associated with titanium dioxide nanoparticles [13,14]. Additionally, it is also used as a pigment in plastics, paper, inks, textiles, photovoltaic cells, biomedical devices, cosmetics, and even as a food additive [7,8].…”