title: Identification of titanium dioxide nanoparticles in food products: induce intracellular oxidative stress mediated by TNF and CYP1A genes in human lung fibroblast cells.
abstract: Food grade TiO2 (E171) is a synthetic additive, and widely used as a coloring agent in many foods, pharmaceutical and personal care products. A few reports have highlighted that insoluble particulates (less than 200nm) of food grade TiO2 are found in many foods and confectionary products. However, information regarding the physico-chemical properties (i.e., size and shape)-based food grade TiO2 nanotoxicity related human health issues are limited. The main goal of this study is to examine the presence of nano-sized particulates and its structural characteristics of food grade- TiO2 materials and to assess the acute cellular uptake and metabolic stress induced by these particulates in human lung fibroblast (WI-38) cells. The results of transmission electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffraction studies indicated that about food grade TiO2 sample contains spherical shaped particulate forms in the nano-scale range, <100nm. The intracellular oxidative stress in human lung fibroblast cells (WI-38) was assessed through studies investigating the cellular uptake of the particles, changes in nuclear and cytoplasmic morphology, intracellular ROS, mitochondrial trans-membrane potential, the cell cycle and the expression of genes linked to metabolic stress markers. Altogether our data clearly indicate that primary metabolic stress indicators such as changes in the intracellular ROS, the dose-dependent loss of the mitochondrial membrane potential, alterations in cell cycle progression (G2/M>S>G0/G1) and changes in the TNF and CYP1A gene expression pattern are linked to cellular stress. Thus, food grade TiO2 as nano-scaled contaminants could not only be potential human health risk factors, suggesting that safety considerations with special respect to a few crucial factors such as size, and shape should be considered and regulated by food regulators.
authors.affiliation: Nanobiotechnology and Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food Science and Agriculture, Riyadh, Saudi Arabia.
authors.forename: Vaiyapuri Subbarayan
authors.initials: VS
authors.lastname: Periasamy
authors.affiliation: Nanobiotechnology and Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food Science and Agriculture, Riyadh, Saudi Arabia.
authors.forename: Jegan
authors.initials: J
authors.lastname: Athinarayanan
authors.affiliation: Nanobiotechnology and Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food Science and Agriculture, Riyadh, Saudi Arabia.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Al-Hadi
authors.affiliation: Nanobiotechnology and Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food Science and Agriculture, Riyadh, Saudi Arabia.
authors.forename: Fahad Al
authors.initials: FA
authors.lastname: Juhaimi
authors.affiliation: Human Nutrition Department, National Research Centre Dokki, Cairo, Egypt.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Mahmoud
authors.affiliation: Nanobiotechnology and Molecular Biology Research Lab, Department of Food Science and Nutrition, College of Food Science and Agriculture, Riyadh, Saudi Arabia. Electronic address: nano.alshatwi@gmail.com.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Alshatwi
mesh_terms: D001692:Biological Transport; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005503:Food Additives / Q000633:toxicity*; D006801:Humans; D008168:Lung / Q000166:cytology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D014025:Titanium / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D004396:Coloring Agents; D005503:Food Additives; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C009495:titanium dioxide; D014025:Titanium; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1
keywords: Antioxidant gene; Food additives; Lung fibroblast cells; Oxidative stress; TiO(2) nanoparticles