Polychlorinated biphenyl-induced effects on metabolic enzymes, AP-1 binding, vitamin E, and oxidative stress in the rat liver

Timothy P. Twaroski, Michelle L. O'Brien, Nicolas Larmonier, Howard P. Glauert, Larry W. Robertson

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Environmental pollutants, such as polychlorinated biphenyls (PCBs), may induce drug metabolism and may be substrates for the induced metabolic enzymes. Both processes may lead to oxidative stress. The goal of this study was to determine the influence of polychlorinated biphenyls, selected as inducers and substrates of drug metabolism, on oxidative events within the liver over a 3-week time course. Male and female Sprague-Dawley rats received two ip injections per week of 4-chlorobiphenyl, 2,4,4′-trichlorobiphenyl, 3,4,5-trichlorobiphenyl, 3,3′,4,4′-tetrachlorobiphenyl (PCB 77), 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB 153), or both PCB 77 and 153 (100 μmol/kg/injection) and were euthanized at the end of 1, 2, or 3 weeks. Hepatic cytochrome P450 1A1 (EROD) activity, DT-diaphorase activity, AP-1 DNA-binding activity, conjugated dienes, and α-tocopherol (vitamin E) as well as α-tocopheryl quinone (oxidized vitamin E) were determined. While the lower chlorinated biphenyls (at these doses and times) showed little or no effect on these oxidative stress parameters, both CYP 1A1 and DT-diaphorase activities were significantly increased in both male and female rats receiving PCB 77, a ligand for the aryl hydrocarbon receptor. In addition, the DNA-binding activity of the transcription factor AP-1 was increased in rats treated with PCB 77 or PCB 153. Within the lipid fraction there was no significant increase observed in conjugated diene concentrations, but there was a significant increase in α-tocopheryl quinone upon treatment with all PCBs tested. These data indicate that α-tocopheryl quinone may be a sensitive marker for PCB exposure and is possibly increased by a wide range of PCBs.

Original languageEnglish (US)
Pages (from-to)85-93
Number of pages9
JournalToxicology and Applied Pharmacology
Volume171
Issue number2
DOIs
StatePublished - Mar 1 2001

Keywords

  • AP-1
  • Cytochrome P-450 1A1
  • DT-diaphorase
  • Polychlorinated biphenyls (PCBs)
  • Vitamin E, and oxidative stress

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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