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ToxSci Advance Access originally published online on September 11, 2003
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Toxicological Sciences 76, 212-219 (2003)
Copyright © 2003 by the Society of Toxicology

SYSTEMS TOXICOLOGY

Dietary Flavonoids Modulate PCB-Induced Oxidative Stress, CYP1A1 Induction, and AhR-DNA Binding Activity in Vascular Endothelial Cells

Pachaikani Ramadass*, Purushothaman Meerarani*, Michal Toborek{dagger}, Larry W. Robertson{ddagger} and Bernhard Hennig*,1

* Molecular and Cell Nutrition Laboratory, College of Agriculture, and {dagger} Department of Surgery, University of Kentucky, Lexington, Kentucky 40546-0215; and {ddagger} Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa 52242

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 µM) or quercetin (10 to 100 µM) with or without PCB 77 (3,3',4,4'-tetrachlorobiphenyl, 3.4 µM) 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 µM and quercetin at 100 µM 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.

Key Words: flavonoids; PCB; oxidative stress; AhR; CYP1A1; vascular endothelial cells.


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