title: Regulation of paraoxonase 1 (PON1) in PCB 126-exposed male Sprague Dawley rats.
abstract: 3,3',4,4',5-Pentachlorobiphenyl (PCB 126), an aryl hydrocarbon receptor (AhR) agonist and most potent dioxin-like PCB congener, significantly alters gene expression, lipid metabolism, and oxidative stress in the liver. PON1, an antioxidant and anti-atherogenic enzyme, is produced in the liver and secreted into the blood where it is incorporated into high density lipoprotein (HDL) and protects LDL and cellular membranes against lipid peroxidation. To explore the regulation of PON1, male Sprague-Dawley rats were treated with ip injections of corn oil or 1 μmol/kg or 5 μmol/kg PCB 126 and euthanized up to two weeks afterwards. Serum total and HDL-cholesterol were increased by low dose and decreased by high dose exposure, while LDL-cholesterol was unchanged. PCB 126 significantly increased hepatic PON1 gene expression and liver and serum PON1 activities. Liver and serum thiobarbituric acid reactive substances levels were not elevated except for high dose and long exposure times. Serum antioxidant capacity was unchanged across all exposure doses and time points. This study, the first describing the regulation of gene expression of PON1 by a PCB congener, raises interesting questions whether elevated PON1 is able to ameliorate PCB 126-induced lipid peroxidation and whether serum PON1 levels may serve as a new biomarker of exposure to dioxin-like compounds.
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, 100 Oakdale Campus, IREH, Iowa City, IA, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Shen
authors.forename: Larry W
authors.initials: LW
authors.lastname: Robertson
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ludewig
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004785:Environmental Pollutants; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D011078:Polychlorinated Biphenyls; D043303:Aryldialkylphosphatase; C023035:3,4,5,3',4'-pentachlorobiphenyl