Dietary flavonoids modulate PCB-induced oxidative stress, CYP1A1 induction, and AhR-DNA binding activity in vascular endothelial cells

Pachaikani Ramadass; Purushothaman Meerarani; Michal Toborek; Larry W Robertson; Bernhard Hennig

doi:10.1093/toxsci/kfg227

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Dietary flavonoids modulate PCB-induced oxidative stress, CYP1A1 induction, and AhR-DNA binding activity in vascular endothelial cells

Journal article

Open access

Peer reviewed

Dietary flavonoids modulate PCB-induced oxidative stress, CYP1A1 induction, and AhR-DNA binding activity in vascular endothelial cells

Pachaikani Ramadass, Purushothaman Meerarani, Michal Toborek, Larry W Robertson and Bernhard Hennig

Toxicological sciences, Vol.76(1), pp.212-219

11/2003

DOI: 10.1093/toxsci/kfg227

PMID: 12970578

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Abstract

Polychlorinated biphenyls (PCBs), especially the more coplanar PCBs, have been shown to induce oxidative stress, various transcription factors, and subsequent inflammatory processes critical to atherosclerosis in vascular endothelial cells. Dietary flavonoids such as catechins and quercetin possess antioxidant and anti-inflammatory properties. To test the hypothesis that flavonoids can modify PCB-mediated endothelial cytotoxicity, endothelial cells were treated with epigallocatechin-3-gallate (EGCG; 5 to 50 muM) or quercetin (10 to 100 muM) with or without PCB 77 (3,3',4,4'-tetrachlorobiphenyl, 3.4 muM) for 6 h. EGCG and quercetin strongly, and in a concentration-dependent manner, inhibited oxidative stress induced by PCB 77 as measured by DCF fluorescence. The role of cytochrome P450 1A1 (CYP1A1) in the PCB-induced toxicity was investigated. EGCG at 50 muM and quercetin at 100 muM concentrations markedly inhibited CYP1A1 mRNA levels and enzyme activity. Furthermore, EGCG and quercetin downregulated the PCB 77-mediated increase in aryl hydrocarbon receptor (AhR)-DNA binding activity. These data suggest that protective effects of EGCG and quercetin are initiated upstream from CYP1A1 and that these flavonoids may be of value for inhibiting the toxic effects of PCBs on vascular endothelial cells.

Endothelial Cells - metabolism

Cells, Cultured

DNA - metabolism

Pulmonary Artery - cytology

Animals

Polychlorinated Biphenyls - toxicity

Quercetin - pharmacology

Swine

Protein Binding - drug effects

Enzyme Induction - drug effects

Receptors, Aryl Hydrocarbon - metabolism

Catechin - analogs & derivatives

Flavonoids - pharmacology

Cytochrome P-450 CYP1A1 - biosynthesis

Oxidative Stress - drug effects

Catechin - pharmacology

Endothelial Cells - enzymology

Endothelial Cells - drug effects

Details

Title: Subtitle: Dietary flavonoids modulate PCB-induced oxidative stress, CYP1A1 induction, and AhR-DNA binding activity in vascular endothelial cells
Creators: Pachaikani Ramadass - Molecular and Cell Nutrition Laboratory, College of Agriculture, University of Kentucky, Lexington 40546-0215, USA
Purushothaman Meerarani
Michal Toborek
Larry W Robertson
Bernhard Hennig
Resource Type: Journal article
Publication Details: Toxicological sciences, Vol.76(1), pp.212-219
Publisher: United States
DOI: 10.1093/toxsci/kfg227
PMID: 12970578
ISSN: 1096-6080
eISSN: 1096-0929
Grant note: P42 ES007380 / NIEHS NIH HHS ES 07380 / NIEHS NIH HHS
Language: English
Date published: 11/2003
Academic Unit: Occupational and Environmental Health
Record Identifier: 9984002327902771

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