open access

https://hdl.handle.net/2115/63978

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

英語

xenobiotic metabolism

2016-01

Wiley-Blackwell

Journal of Food Science

81(1)

T275-T281

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.

学術雑誌論文

Accepted Manuscript

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.

0022-1147

1750-3841

AA00698289