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

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.

• Authors: Ian K Lai, Yingtao Chai, Donald Simmons, Walter H Watson, Rommel Tan, Wanda M Haschek, Kai Wang, Bingxuan Wang, Gabriele Ludewig, Larry W Robertson
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 124 Issue 1 Pg. 202-14 (Nov 2011) ISSN: 1096-0929 [Electronic] United States
• PMID: 21865291 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antioxidants
• Receptors, Aryl Hydrocarbon
• Selenium Compounds
• Polychlorinated Biphenyls
• Cytochrome P-450 CYP1A1
• Selenic Acid
• 3,4,5,3',4'-pentachlorobiphenyl

Topics

• Administration, Oral
• Animals
• Antioxidants (administration & dosage, therapeutic use)
• Chemical and Drug Induced Liver Injury (enzymology, etiology, pathology, prevention & control)
• Cytochrome P-450 CYP1A1 (metabolism)
• Dose-Response Relationship, Drug
• Drug Interactions
• Liver (drug effects, enzymology, pathology)
• Male
• Organ Size (drug effects)
• Organ Specificity
• Oxidation-Reduction
• Polychlorinated Biphenyls (toxicity)
• Rats
• Rats, Sprague-Dawley
• Receptors, Aryl Hydrocarbon (agonists)
• Selenic Acid
• Selenium Compounds (administration & dosage, pharmacokinetics, therapeutic use)