Linked Life Data

10630576

Source:http://linkedlifedata.com/resource/pubmed/id/10630576

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-2-10
pubmed:abstractText
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:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Albumins, http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants, http://linkedlifedata.com/resource/pubmed/chemical/Benzoflavones, http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Polychlorinated Biphenyls, http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolidines, http://linkedlifedata.com/resource/pubmed/chemical/Thiocarbamates, http://linkedlifedata.com/resource/pubmed/chemical/Vitamin E, http://linkedlifedata.com/resource/pubmed/chemical/alpha-naphthoflavone, http://linkedlifedata.com/resource/pubmed/chemical/pyrrolidine dithiocarbamic acid
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
232-9
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Antioxidant protection against PCB-mediated endothelial cell activation.
pubmed:affiliation
Department of Nutrition and Food Science, Graduate Center for Toxicology, University of Kentucky, Lexington 40506-0054, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't