Oxidative stress induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin is mediated by the aryl hydrocarbon (Ah) receptor complex

N. Z. Alsharif, T. Lawson, S. J. Stohs

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

The toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its bioisosteres involves binding to a specific TCDD (Aryl hydrocarbon (Ah)) receptor, interaction of this complex with chromatin, and the ultimate production of a pleiotropic response. The mechanism whereby toxic effects are produced following interaction of TCDD with the receptor complex is not known. Oxidative stress (OS) may play an important role in expression of the toxic manifestations of TCDD. TCDD has been shown to produce a dose- and time-dependent increase in superoxide anion from peritoneal lavage cells (PLC) (primarily macrophage). Therefore, to determine if TCDD-induced production of superoxide anion by PLC is mediated through the Ah receptor, congenic mice were used which differ at the Ah locus. One day after the administration of 5, 25, 50 or 125 μg TCDD/kg p.o. as a single dose, 1.4-, 1.7-, 4.3- and 3.5-fold increases, respectively, occurred in superoxide anion production by PLC from the TCDD-responsive C57BL/6J (bb) mice relative to control cells. However, only 125 μg TCDD/kg produced a significant increase in superoxide anion formation with PLC from the non-responsive C57BL/6J (dd) strain of mice (1.7-fold increase). The role of the Ah receptor was further evaluated by utilizing the TCDD-resistant DBA/2 strain of mice, two TCDD congeners and in vitro studies. The combined results indicate that TCDD produces and oxidative stress in mice as measured by production of superoxide anion, and this effect is controlled in part by the Ah receptor complex.

Original languageEnglish (US)
Pages (from-to)39-51
Number of pages13
JournalToxicology
Volume92
Issue number1-3
DOIs
StatePublished - Sep 6 1994

Keywords

  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin
  • Ah receptor
  • Oxidative stress
  • Peritoneal lavage cells
  • Reactive oxygen species
  • TCDD-responsive C57BL/6J (bb) and non-responsive C57BL/6J (dd) mice

ASJC Scopus subject areas

  • Toxicology

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