title: Constitutive Effects of Lead on Aryl Hydrocarbon Receptor Gene Battery and Protection by β-carotene and Ascorbic Acid in Human HepG2 Cells.
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.
authors.affiliation: Laboratory of Toxicology, Dept. of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido Univ, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
authors.forename: Wageh S
authors.initials: WS
authors.lastname: Darwish
authors.affiliation: Laboratory of Toxicology, Dept. of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido Univ, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ikenaka
authors.affiliation: Laboratory of Toxicology, Dept. of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido Univ, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
authors.forename: Shouta M M
authors.initials: SM
authors.lastname: Nakayama
authors.affiliation: Laboratory of Toxicology, Dept. of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido Univ, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
authors.forename: Hazuki
authors.initials: H
authors.lastname: Mizukawa
authors.affiliation: Food Control Dept, Faculty of Veterinary Medicine, Zagazig Univ, Zagazig, 44510, Egypt.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ishizuka
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects; D004785:Environmental Pollutants / Q000009:adverse effects; D014453:Glucuronosyltransferase / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008658:Inactivation, Metabolic / Q000187:drug effects; D007854:Lead / Q000009:adverse effects*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D015262:Xenobiotics / Q000009:adverse effects; D019207:beta Carotene / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D004785:Environmental Pollutants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018336:Receptors, Aryl Hydrocarbon; D015262:Xenobiotics; D019207:beta Carotene; D007854:Lead; C569463:CYP1A1 protein, human; C504573:CYP1A2 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D051547:Heme Oxygenase-1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase; D001205:Ascorbic Acid
keywords: AhR; ascorbic acid; lead; xenobiotic metabolism; β-carotene