Antioxidant protection against PCB-mediated endothelial cell activation

R. Slim, M. Toborek, L. W. Robertson, B. Hennig

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Certain environmental contaminants such as polyhalogenated aromatic hydrocarbons may be implicated in diseases of the vasculature by compromising normal functions of vascular endothelial cells. We have shown previously that 3,3',4,4'-tetrachlorobiphenyl (PCB 77), an aryl hydrocarbon (Ah) receptor agonist, can cause disruption of endothelial barrier function. This was supported by an increase in oxidative stress as measured by enhanced 2',7'- dichlorofluorescein (DCF) fluorescence and activation of the oxidative stress-sensitive transcription factor NF-κB. We have now tested the protective effects of antioxidants vitamin E (α-tocopherol) and pyrrolidine dithiocarbamate (PDTC) on endothelial cell activation induced by PCB 77. Only vitamin E completely blocked PCB 77-mediated endothelial barrier dysfunction. This protective effect by vitamin E was associated with a decrease in both oxidative stress, as measured by DCF fluorescence, as well as in NF-κB activation. Furthermore, vitamin E decreased PCB 77-mediated production of the inflammatory cytokine IL-6. Although pretreatment of endothelial cells with PDTC prevented the induction of NF-κB by PCB 77, this inhibition was not associated with a decrease in DCF levels or protection against endothelial barrier dysfunction. Pretreatment with α-naphthoflavone (α-NF), an Ah receptor partial antagonist and specific inhibitor of cytochrome P450 1A, partially protected against PCB 77-induced endothelial barrier dysfunction. This observation was paralleled by the fact that α-NF did not fully antagonize the PCB-induced increase in DCF in endothelial cells. Furthermore, PCB-mediated induction of NF-κB and production of IL-6 were only partially blocked by α-NF. Of all the tested compounds (vitamin E, PDTC and α-NF), vitamin E was most potent in blocking PCB 77-mediated endothelial cell activation. These data give an insight into the potential use of vitamin E and related antioxidants to limit PCB-mediated cell injury and into the use of α-NF to explore mechanisms underlying the injurious potential of Ah receptor agonists.

Original languageEnglish (US)
Pages (from-to)232-239
Number of pages8
JournalToxicological Sciences
Volume52
Issue number2
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Atherosclerosis
  • Disease
  • Endothelial cells
  • Environmental contaminants
  • Nutrition
  • Oxidative stress
  • Polychlorinated biphenyls
  • Vitamin E

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'Antioxidant protection against PCB-mediated endothelial cell activation'. Together they form a unique fingerprint.

Cite this