TCDD-induced CYP1A1 expression, an index of dioxin toxicity, is suppressed by flavonoids permeating the human intestinal Caco-2 cell monolayers.
Since the toxicological effects of dioxins are mainly mediated by the aryl hydrocarbon receptor (AhR), an in vitro assessment system for AhR activity was used in this study to search for flavonoids that attenuated dioxin toxicity through the intestinal epithelial monolayer. When AhR transformation in Hepa-1c1c7 cells was examined by southwestern ELISA, nine flavonoids among 34 kinds of flavonoids inhibited the transformation by more than one-half. When each flavonoid with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was added to dioxin-responsive HepG2 cells, seven flavonoids significantly restrained the TCDD-induced transcriptional activity of the CYP1A1 promoter. Furthermore, those seven flavonoids that had permeated the Caco-2 cell monolayers demonstrated an inhibitory effect on both the AhR transformation and on the transcriptional activity of the CYP1A1 promoter. The expression level of the CYP1A1 mRNA and protein induced by TCDD was suppressed by flavone, galangin, and tangeretin. It is proposed from these results that some flavonoids have the ability to suppress dioxin-induced AhR activity after permeating the human intestinal epithelial cell monolayer.
Hamada
Mika
M
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Yayoi, Bunkyo-ku, 113-8657, Japan. aa56067@mail.ecc.u-tokyo.ac.jp
Satsu
Hideo
H
Natsume
Yayoi
Y
Nishiumi
Shin
S
Fukuda
Itsuko
I
Ashida
Hitoshi
H
Shimizu
Makoto
M
D018938:Caco-2 Cells; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005419:Flavonoids; D000072317:Polychlorinated Dibenzodioxins; D019363:Cytochrome P-450 CYP1A1