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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Antioxidant protection against PCB-mediated endothelial cell activation.

Authors: Slim, R; Toborek, M; Robertson, L W; Hennig, B

Published In Toxicol Sci, (1999 Dec)

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-kappaB. We have now tested the protective effects of antioxidants vitamin E (alpha-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-kappaB 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-kappaB by PCB 77, this inhibition was not associated with a decrease in DCF levels or protection against endothelial barrier dysfunction. Pretreatment with alpha-naphthoflavone (alpha-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 alpha-NF did not fully antagonize the PCB-induced increase in DCF in endothelial cells. Furthermore, PCB-mediated induction of NF-kappaB and production of IL-6 were only partially blocked by alpha-NF. Of all the tested compounds (vitamin E, PDTC and alpha-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 alpha-NF to explore mechanisms underlying the injurious potential of Ah receptor agonists.

PubMed ID: 10630576 Exiting the NIEHS site

MeSH Terms: Albumins/metabolism; Animals; Antioxidants/pharmacology*; Benzoflavones/pharmacology; Carcinogens/antagonists & inhibitors*; Carcinogens/chemical synthesis; Carcinogens/toxicity*; Cell Nucleus/drug effects; Cell Nucleus/metabolism; Cytosol/drug effects; Cytosol/metabolism; Electrophoresis; Endothelium, Vascular/cytology*; Interleukin-6/biosynthesis; NF-kappa B/antagonists & inhibitors; NF-kappa B/metabolism; Oxidative Stress/drug effects; Polychlorinated Biphenyls/antagonists & inhibitors*; Polychlorinated Biphenyls/chemical synthesis; Polychlorinated Biphenyls/toxicity*; Pyrrolidines/pharmacology; Swine; Thiocarbamates/pharmacology; Vitamin E/pharmacology

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