title: Suppressive effect of enzymatically modified isoquercitrin on phenobarbital-induced liver tumor promotion in rats.
abstract: To investigate the effect of enzymatically modified isoquercitrin (EMIQ) on hepatocellular tumor promotion induced by phenobarbital (PB), male rats were administered a single intraperitoneal injection of 200 mg/kg N-diethylnitrosamine (DEN) and then fed with a diet containing PB (500 ppm) for 8 weeks, with or without EMIQ (2,000 ppm) in the drinking water. One week after PB administration, rats underwent a two-thirds partial hepatectomy. The PB-induced increase in the number and area of glutathione S-transferase placental form-positive foci and the proliferating cell nuclear antigen-positive ratio was significantly suppressed by EMIQ. Real-time reverse transcription-polymerase chain reaction analysis revealed increases in mRNA expression levels of Cyp2b2 and Mrp2 in the DEN-PB and DEN-PB-EMIQ groups compared with the DEN-alone group, while the level of Mrp2 decreased in the DEN-PB-EMIQ group compared with the DEN-PB group. There were no significant changes in microsomal reactive oxygen species (ROS) production and oxidative stress markers between the DEN-PB and DEN-PB-EMIQ groups. Immunohistochemically, the constitutive active/androstane receptor (CAR) in the DEN-PB group was clearly localized in the nuclei, but its immunoreactive intensity was decreased in the DEN-PB-EMIQ group. These results indicate that EMIQ suppressed the liver tumor-promoting activity of PB by inhibiting nuclear translocation of CAR, and not by suppression of oxidative stress.
authors: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo, Japan.
authors: Reiko
authors: R
authors: Morita
authors: Keisuke
authors: K
authors: Shimamoto
authors: Yuji
authors: Y
authors: Ishii
authors: Kazunori
authors: K
authors: Kuwata
authors: Bun-ichiro
authors: B
authors: Ogawa
authors: Masako
authors: M
authors: Imaoka
authors: Shim-mo
authors: SM
authors: Hayashi
authors: Kazuhiko
authors: K
authors: Suzuki
authors: Makoto
authors: M
authors: Shibutani
authors: Kunitoshi
authors: K
authors: Mitsumori
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis / Q000378:metabolism; D000090702:Constitutive Androstane Receptor; D004052:Diethylnitrosamine / Q000633:toxicity; D060766:Drinking Water / Q000737:chemistry; D005982:Glutathione Transferase / Q000378:metabolism; D006498:Hepatectomy; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010634:Phenobarbital / Q000633:toxicity*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000032:analysis / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; C423013:Abcc2 protein, rat; D016588:Anticarcinogenic Agents; D000090702:Constitutive Androstane Receptor; D060766:Drinking Water; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; C016527:isoquercitrin; D004052:Diethylnitrosamine; D011794:Quercetin; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C025619:steroid 16-beta-hydroxylase; D005982:Glutathione Transferase; D010634:Phenobarbital