Toxicity and cellular responses of intestinal cells exposed to titanium dioxide

Abstract

The increasing use of nanomaterials in healthcare and industrial products heightens the possibility of their ingestion by humans, other mammals, and fish. While toxicity of many nanomaterials has recently been studied, reports of non-lethal effects of nanomaterials remain ill-defined. This study investigates possible pathways by which nanoparticles, titanium dioxide (TiO(2)), could cross the epithelium layer by employing both toxicity and mechanistic studies. This study provides evidence that at 10 microg/mL and above, TiO(2) nanoparticles cross the epithelial lining of the intestinal model by transcytosis, albeit at low levels. TiO(2) was able to penetrate into and through the cells without disrupting junctional complexes, as measured by gamma-catenin. To monitor the epithelial integrity, transepithelial electrical resistance (TEER) was employed and determined low concentrations (10 or 100 microg/mL) of TiO(2) do not disrupt epithelial integrity. Live/dead analysis results did not show cell death after exposure to TiO(2). In addition, at 10 microg/mL (and above) TiO(2) nanoparticles begin alteration of both microvillar organization on the apical surface of the epithelium as well as induce a rise in intracellular-free calcium. The latter is a mechanism cells use to respond to extracellular stimuli and may be linked to the alteration of the apical microvilli. Although TiO(2) does not show cell death, the implication of other, non-lethal, effects could lead to undesired outcomes (i.e., disease, malnutrition, shortened life span, etc.).

Investigation of the Cytotoxic Effects of Titanate Nanotubes on Caco-2 Cells

“…2). This is in accordance with the findings that titanium dioxide (TiO 2 ) nanoparticles at 1 mg/ml did not cause the death of Caco-2 cells (11) and that titania nanotubes up to 1.1 mg/ml are non-cytotoxic on A549 lung epithelial cells (12).…”

“…These granules may be titanium dioxide particles formed from the nanotubes during the incubation or TiO 2 impurities. This is in accordance with a previous report that at ≥10 μg/ml, TiO 2 nanoparticles are able to enter Caco-2 cells and cross a Caco-2 monolayer by transcytosis (11). Caco-2 cells were treated with nanotubes and titanium dioxide in different concentrations for 120 min, and their viability was determined by MTT tests.…”

Interaction of SiO2 nanoparticles with neuronal cells: Ionic mechanisms involved in the perturbation of calcium homeostasis

“…Apart from silica NPs , data on the perturbations of calcium signaling mechanisms induced by NPs are still scarce (see e.g. Huang et al, 2010;Koeneman et al, 2010) and this is particularly true for neuronal cells (Guo et al, 2013;Haase et al, 2012;Nyitrai et al, 2013;Tang et al, 2008aTang et al, , 2008b, as recently reviewed (Lovisolo et al, 2014).…”

Utility of models of the gastrointestinal tract for assessment of the digestion and absorption of engineered nanomaterials released from food matrices

“…The permeability of 40 nm titanium dioxide NMs was also determined with Caco-2 cells using a dual chamber approach (Koeneman et al, 2010). The average diameter of the NMs in the donor medium was greater than 500 nm, indicating agglomeration.…”