title: Antagonistic and agonistic effects of indigoids on the transformation of an aryl hydrocarbon receptor.
abstract: Halogenated and polycyclic aromatic hydrocarbons, exogenous ligands of the aryl hydrocarbon receptor (AhR), cause various toxicological effects through the transformation of the AhR. In this study, we investigated the antagonistic effects of indigoids on the transformation in addition to their agonistic ones. In a cell-free system, indigoids induced the transformation dose-dependently, but suppressed the transformation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin and the binding of 3-methylcholanthrene to the AhR. In mouse hepatoma Hepa-1c1c7 cells, indigoids, especially indirubin, suppressed the transformation and expression of CYP1A1 by inhibiting the translocation of AhR into the nucleus. When orally administered to mice at 10mg/kg BW/day for three successive days, indigoids did not induce AhR transformation and expression of the CYP1A subfamily in the liver, while indirubin and indigo upregulated quinone reductase activity. These results indicate that indigoids are able to bind to the AhR as ligands and exhibit antagonistic effects at lower concentrations in mammalian cells.
authors: Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan.
authors: Shin
authors: S
authors: Nishiumi
authors: Norio
authors: N
authors: Yamamoto
authors: Rie
authors: R
authors: Kodoi
authors: Itsuko
authors: I
authors: Fukuda
authors: Ken-ichi
authors: K
authors: Yoshida
authors: Hitoshi
authors: H
authors: Ashida
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D007203:Indigo Carmine; D007211:Indoles / Q000008:administration & dosage*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010881:Piperidones / Q000008:administration & dosage; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D007211:Indoles; D010881:Piperidones; D018336:Receptors, Aryl Hydrocarbon; C446045:indigoidine; C049010:isoindigotin; D007203:Indigo Carmine; C027185:indirubin