Dietary selenium as a modulator of PCB 126-induced hepatotoxicity in male Sprague-Dawley rats

Ian K Lai; Yingtao Chai; Donald Simmons; Walter H Watson; Rommel Tan; Wanda M Haschek; Kai Wang; Bingxuan Wang; Gabriele Ludewig; Larry W Robertson

doi:10.1093/toxsci/kfr215

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Dietary selenium as a modulator of PCB 126-induced hepatotoxicity in male Sprague-Dawley rats

Journal article

Open access

Peer reviewed

Dietary selenium as a modulator of PCB 126-induced hepatotoxicity in male Sprague-Dawley rats

Ian K Lai, Yingtao Chai, Donald Simmons, Walter H Watson, Rommel Tan, Wanda M Haschek, Kai Wang, Bingxuan Wang, Gabriele Ludewig and Larry W Robertson

Toxicological sciences, Vol.124(1), pp.202-214

11/2011

DOI: 10.1093/toxsci/kfr215

PMCID: PMC3196656

PMID: 21865291

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Abstract

Homeostasis of selenium (Se), a critical antioxidant incorporated into amino acids and enzymes, is disrupted by exposure to aryl hydrocarbon receptor (AhR) agonists. Here we examined the importance of dietary Se in preventing the toxicity of the most toxic polychlorinated biphenyl congener, 3,3',4,4',5-pentachlorobiphenyl (PCB 126), a potent AhR agonist. Male Sprague-Dawley rats were fed a modified AIN-93 diet with differing dietary Se levels (0.02, 0.2, and 2 ppm). Following 3 weeks of acclimatization, rats from each dietary group were given a single ip injection of corn oil (vehicle), 0.2, 1, or 5 μmol/kg body weight PCB 126, followed 2 weeks later by euthanasia. PCB exposure caused dose-dependent increases in liver weight and at the highest PCB 126 dose decreases in whole body weight gains. Hepatic cytochrome P-450 (CYP1A1) activity was significantly increased even at the lowest dose of PCB 126, indicating potent AhR activation. PCB exposure diminished hepatic Se levels in a dose-dependent manner, and this was accompanied by diminished Se-dependent glutathione peroxidase activity. Both these effects were partially mitigated by Se supplementation. Conversely, thioredoxin (Trx) reductase activity and Trx oxidation state, although significantly diminished in the lowest dietary Se groups, were not affected by PCB exposure. In addition, PCB 126-induced changes in hepatic copper, iron, manganese, and zinc were observed. These results demonstrate that supplemental dietary Se was not able to completely prevent the toxicity caused by PCB 126 but was able to increase moderately the levels of several key antioxidants, thereby maintaining them roughly at normal levels.

Liver - pathology

Liver - enzymology

Male

Dose-Response Relationship, Drug

Drug Interactions

Liver - drug effects

Selenium Compounds - pharmacokinetics

Chemical and Drug Induced Liver Injury - pathology

Chemical and Drug Induced Liver Injury - enzymology

Chemical and Drug Induced Liver Injury - etiology

Chemical and Drug Induced Liver Injury - prevention & control

Oxidation-Reduction

Administration, Oral

Rats

Cytochrome P-450 CYP1A1 - metabolism

Organ Specificity

Rats, Sprague-Dawley

Receptors, Aryl Hydrocarbon - agonists

Selenic Acid

Antioxidants - therapeutic use

Organ Size - drug effects

Animals

Polychlorinated Biphenyls - toxicity

Selenium Compounds - administration & dosage

Antioxidants - administration & dosage

Selenium Compounds - therapeutic use

Details

Title: Subtitle: Dietary selenium as a modulator of PCB 126-induced hepatotoxicity in male Sprague-Dawley rats
Creators: Ian K Lai - Interdisciplinary Graduate Program in Human Toxicology, College of Public Health, University of Iowa, Iowa City, Iowa 52242, USA
Yingtao Chai
Donald Simmons
Walter H Watson
Rommel Tan
Wanda M Haschek
Kai Wang
Bingxuan Wang
Gabriele Ludewig
Larry W Robertson
Resource Type: Journal article
Publication Details: Toxicological sciences, Vol.124(1), pp.202-214
Publisher: United States
DOI: 10.1093/toxsci/kfr215
PMID: 21865291
PMCID: PMC3196656
ISSN: 1096-6080
eISSN: 1096-0929
Grant note: P30 ES005605 / NIEHS NIH HHS P30 ES05605 / NIEHS NIH HHS P42 ES013661 / NIEHS NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 11/2011
Academic Unit: Occupational and Environmental Health; Biostatistics; Iowa Superfund Research Program
Record Identifier: 9983997453702771

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29 Times Cited - Web of Science