title: Assessment of the Mitigative Capacity of Dietary Zinc on PCB126 Hepatotoxicity and the Contribution of Zinc to Toxicity.
abstract: Hepatic levels of the essential micronutrient, zinc, are diminished by several hepatotoxicants, and the dietary supplementation of zinc has proven protective in those cases. 3,3',4,4',5-Pentachlorobiphenyl (PCB126), a liver toxicant, alters hepatic nutrient homeostasis and lowers hepatic zinc levels. The current study was designed to determine the mitigative potential of dietary zinc in the toxicity associated with PCB126 and the role of zinc in that toxicity. Male Sprague-Dawley rats were divided into three dietary groups and fed diets deficient in zinc (7 ppm Zn), adequate in zinc (30 ppm Zn), and supplemented in zinc (300 ppm). The animals were maintained for 3 weeks on these diets, then given a single IP injection of vehicle or 1 or 5 μmol/kg PCB126. After 2 weeks, the animals were euthanized. Dietary zinc increased the level of ROS, the activity of CuZnSOD, and the expression of metallothionein but decreased the levels of hepatic manganese. PCB126 exposed rats exhibited classic signs of exposure, including hepatomegaly, increased hepatic lipids, increased ROS and CYP induction. Liver histology suggests some mild ameliorative properties of both zinc deficiency and zinc supplementation. Other metrics of toxicity (relative liver and thymus weights, hepatic lipids, and hepatic ROS) did not support this trend. Interestingly, the zinc supplemented high dose PCB126 group had mildly improved histology and less efficacious induction of investigated genes than did the low dose PCB126 group. Overall, decreases in zinc caused by PCB126 likely contribute little to the ongoing toxicity, and the mitigative/preventive capacity of zinc against PCB126 exposure seems limited.
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa , Iowa City, Iowa 52242, United States.|Department of Occupational and Environmental Health, College of Public Health, University of Iowa , Iowa City, Iowa 52242, United States.
authors.forename: William D
authors.initials: WD
authors.lastname: Klaren
authors.affiliation: Department of Pathology, University of Iowa , Iowa City, Iowa 52242, United States.
authors.forename: Katherine N
authors.initials: KN
authors.lastname: Gibson-Corley
authors.affiliation: State Hygienic Laboratory, University of Iowa , Ankeny, Iowa 50023, United States.
authors.forename: Brian
authors.initials: B
authors.lastname: Wels
authors.affiliation: State Hygienic Laboratory, University of Iowa , Ankeny, Iowa 50023, United States.
authors.forename: Donald L
authors.initials: DL
authors.lastname: Simmons
authors.affiliation: Free Radical and Radiation Biology Program, University of Iowa Carver College of Medicine , Iowa City, Iowa 52242, United States.
authors.forename: Michael L
authors.initials: ML
authors.lastname: McCormick
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa , Iowa City, Iowa 52242, United States.|Free Radical and Radiation Biology Program, University of Iowa Carver College of Medicine , Iowa City, Iowa 52242, United States.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Spitz
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa , Iowa City, Iowa 52242, United States.|Department of Occupational and Environmental Health, College of Public Health, University of Iowa , Iowa City, Iowa 52242, United States.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Robertson
mesh_terms: D000818:Animals; D004032:Diet; D005247:Feeding Behavior; D015870:Gene Expression; D008099:Liver / Q000187:drug effects*; D008297:Male; D008668:Metallothionein / Q000235:genetics; D018384:Oxidative Stress; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018336:Receptors, Aryl Hydrocarbon; D008668:Metallothionein; D011078:Polychlorinated Biphenyls; D013482:Superoxide Dismutase; D015032:Zinc; C023035:3,4,5,3',4'-pentachlorobiphenyl