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Constitutive Effects of Lead on Aryl Hydrocarbon Receptor Gene Battery and Protection by beta-carotene and Ascorbic Acid in Human HepG2 Cells

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J. Food Sci. v.81(1)p.T275-T281.pdf349.24 kBPDFView/Open
Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/63978

Title: Constitutive Effects of Lead on Aryl Hydrocarbon Receptor Gene Battery and Protection by beta-carotene and Ascorbic Acid in Human HepG2 Cells
Authors: Darwish, Wageh S. Browse this author
Ikenaka, Yoshinori Browse this author →KAKEN DB
Nakayama, Shouta M. M. Browse this author →KAKEN DB
Mizukawa, Hazuki Browse this author →KAKEN DB
Ishizuka, Mayumi Browse this author →KAKEN DB
Keywords: AhR
ascorbic acid
beta-carotene
lead
xenobiotic metabolism
Issue Date: Jan-2016
Publisher: Wiley-Blackwell
Journal Title: Journal of Food Science
Volume: 81
Issue: 1
Start Page: T275
End Page: T281
Publisher DOI: 10.1111/1750-3841.13162
Abstract: Lead (Pb) is an environmental pollutant that can get entry into human body through contaminated foods, drinks, and inhaled air leading to severe biological consequences, and has been responsible for many deaths worldwide. The objectives of this study were 1st to investigate the modulatory effects of environmentally relevant concentrations of Pb on AhR gene battery, which is controlling xenobiotics metabolism. 2nd, trials to reduce Pb-induced adverse effects were done using some phytochemicals like beta-carotene or ascorbic acid. Human hepatoma (HepG2) cell lines were exposed to a wide range of Pb concentrations varying from physiological to toxic levels (0 to 10 mg/L) for 24 h. High Pb concentrations (1 to 10 mg/L) significantly reduced phase I (CYP1A1 and 1A2) and phase II (UGT1A6 and NQO1) xenobiotic metabolizing enzyme mRNA expression in a mechanistic manner through the AhR regulation pathway. Additionally, these Pb concentrations induced oxidative stress in HepG2 cells in terms of production of reactive oxygen species (ROS) and induced heme oxygenase-1 mRNA expression in a concentration-dependent phenomenon. Coexposure of HepG2 cells to physiological concentrations of some micronutrients, like beta-carotene (10 mu M) or ascorbic acid (0.1 mM), along with Pb (1 mg/L) for 24 h significantly reduced the levels of ROS production and recovered AhR mRNA expression into the normal levels. Thus, consumption of foods rich in these micronutrients may help to reduce the adverse effects of lead in areas with high levels of pollution.
Rights: This is the peer reviewed version of the following article: Darwish WS, Ikenaka Y, Nakayama SMM, Mizukawa H, Ishizuka M. 2016. Constitutive Effects of Lead on Aryl Hydrocarbon Receptor Gene Battery and Protection by β-carotene and Ascorbic Acid in Human HepG2 Cells. J Food Sci 81:T275-81, which has been published in final form at http://dx.doi.org/10.1111/1750-3841.13162. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Type: article (author version)
URI: http://hdl.handle.net/2115/63978
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 石塚 真由美

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