Dietary flavonoids modulate PCB-induced oxidative stress, CYP1A1 induction, and AhR-DNA binding activity in vascular endothelial cells.
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.
Ramadass
Pachaikani
P
Molecular and Cell Nutrition Laboratory, College of Agriculture, University of Kentucky, Lexington 40546-0215, USA.
Meerarani
Purushothaman
P
Toborek
Michal
M
Robertson
Larry W
LW
Hennig
Bernhard
B
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D004247:DNA / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011485:Protein Binding / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology; D011794:Quercetin / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D013552:Swine
D005419:Flavonoids; D018336:Receptors, Aryl Hydrocarbon; D002392:Catechin; D004247:DNA; D011794:Quercetin; C045651:epigallocatechin gallate; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C028451:3,4,3',4'-tetrachlorobiphenyl