RRC ID 39053
著者 Darwish WS, Ikenaka Y, Nakayama SM, Mizukawa H, Ishizuka M.
タイトル Constitutive Effects of Lead on Aryl Hydrocarbon Receptor Gene Battery and Protection by β-carotene and Ascorbic Acid in Human HepG2 Cells.
ジャーナル J Food Sci
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 β-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 β-carotene (10 μM) 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.
巻・号 81(1)
ページ T275-81
公開日 2016-1-1
DOI 10.1111/1750-3841.13162
PMID 26630500
MeSH Antioxidants / pharmacology* Ascorbic Acid / pharmacology* Cytochrome P-450 CYP1A1 / metabolism Cytochrome P-450 CYP1A2 / metabolism Environmental Exposure / adverse effects Environmental Pollutants / adverse effects Glucuronosyltransferase / metabolism Heme Oxygenase-1 / genetics Heme Oxygenase-1 / metabolism Hep G2 Cells Humans Inactivation, Metabolic / drug effects Lead / adverse effects* NAD(P)H Dehydrogenase (Quinone) / metabolism Oxidative Stress / drug effects* RNA, Messenger / metabolism Reactive Oxygen Species / metabolism* Receptors, Aryl Hydrocarbon / genetics Receptors, Aryl Hydrocarbon / metabolism* Xenobiotics / adverse effects beta Carotene / pharmacology*
IF 2.479
引用数 16
WOS 分野 FOOD SCIENCE & TECHNOLOGY
リソース情報
ヒト・動物細胞 Hep G2(RCB1886)