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 (TiO2), could cross the epithelium layer by employing both toxicity and mechanistic studies. This study provides evidence that at 10 μg/mL and above, TiO2 nanoparticles cross the epithelial lining of the intestinal model by transcytosis, albeit at low levels. TiO2 was able to penetrate into and through the cells without disrupting junctional complexes, as measured by γ-catenin. To monitor the epithelial integrity, transepithelial electrical resistance (TEER) was employed and determined low concentrations (10 or 100 μg/mL) of TiO2 do not disrupt epithelial integrity. Live/dead analysis results did not show cell death after exposure to TiO2. In addition, at 10 μg/mL (and above) TiO2 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 TiO2 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.).
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Abbreviations
- TiO2 :
-
titanium dioxide
- TEER:
-
transepithelial electrical resistance
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Acknowledgments
The authors are grateful for funding from the U.S. Environmental Protection Agency. The authors thank the W.M. Keck Bioimaging Laboratory and the Electron Microscope Laboratory in the School of Life Sciences Bioimaging Facility at Arizona State University managed by Bret Judson and David Lowry, respectively.
Although the research described in this article has been funded wholly or in part by the United States Environmental Protection Agency through grant/cooperative agreement RD831713 to Arizona State University, it has not been subjected to the Agency's required peer and policy review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred.
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Koeneman, B.A., Zhang, Y., Westerhoff, P. et al. Toxicity and cellular responses of intestinal cells exposed to titanium dioxide. Cell Biol Toxicol 26, 225–238 (2010). https://doi.org/10.1007/s10565-009-9132-z
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DOI: https://doi.org/10.1007/s10565-009-9132-z