Journal article
Assessment of the Mitigative Capacity of Dietary Zinc on PCB126 Hepatotoxicity and the Contribution of Zinc to Toxicity
Chemical research in toxicology, Vol.29(5), pp.851-859
05/16/2016
DOI: 10.1021/acs.chemrestox.6b00022
PMCID: PMC5100827
PMID: 26967026
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.
Details
- Title: Subtitle
- Assessment of the Mitigative Capacity of Dietary Zinc on PCB126 Hepatotoxicity and the Contribution of Zinc to Toxicity
- Creators
- William D Klaren - Department of Occupational and Environmental Health, College of Public Health, University of Iowa , Iowa City, Iowa 52242, United StatesKatherine N Gibson-Corley - Department of Pathology, University of Iowa , Iowa City, Iowa 52242, United StatesBrian Wels - State Hygienic Laboratory, University of Iowa , Ankeny, Iowa 50023, United StatesDonald L Simmons - State Hygienic Laboratory, University of Iowa , Ankeny, Iowa 50023, United StatesMichael L McCormick - Free Radical and Radiation Biology Program, University of Iowa Carver College of Medicine , Iowa City, Iowa 52242, United StatesDouglas R Spitz - Free Radical and Radiation Biology Program, University of Iowa Carver College of Medicine , Iowa City, Iowa 52242, United StatesLarry W Robertson - Department of Occupational and Environmental Health, College of Public Health, University of Iowa , Iowa City, Iowa 52242, United States
- Resource Type
- Journal article
- Publication Details
- Chemical research in toxicology, Vol.29(5), pp.851-859
- DOI
- 10.1021/acs.chemrestox.6b00022
- PMID
- 26967026
- PMCID
- PMC5100827
- NLM abbreviation
- Chem Res Toxicol
- ISSN
- 0893-228X
- eISSN
- 1520-5010
- Publisher
- United States
- Grant note
- P30 ES005605 / NIEHS NIH HHS R01 CA182804 / NCI NIH HHS P42 ES013661 / NIEHS NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 05/16/2016
- Academic Unit
- Occupational and Environmental Health; Pathology; Radiation Oncology; Iowa Superfund Research Program; Ophthalmology and Visual Sciences
- Record Identifier
- 9984002485802771
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