caa a22 4500 445854081 CHVBK 20180317145423.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s00204-011-0696-z doi (NATIONALLICENCE)springer-10.1007/s00204-011-0696-z Suppressive effect of enzymatically modified isoquercitrin on phenobarbital-induced liver tumor promotion in rats [Elektronische Daten] [Reiko Morita, Keisuke Shimamoto, Yuji Ishii, Kazunori Kuwata, Bun-ichiro Ogawa, Masako Imaoka, Shim-mo Hayashi, Kazuhiko Suzuki, Makoto Shibutani, Kunitoshi Mitsumori] 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 200mg/kgN-diethylnitrosamine (DEN) and then fed with a diet containing PB (500ppm) for 8weeks, with or without EMIQ (2,000ppm) 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. Springer-Verlag, 2011 Enzymatically modified isoquercitrin nationallicence Phenobarbital nationallicence Reactive oxygen species nationallicence CYP2B inducer nationallicence Liver tumor nationallicence Rat nationallicence Morita Reiko Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut Shimamoto Keisuke Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut Ishii Yuji Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, 158-8501, Tokyo, Japan aut Kuwata Kazunori Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut Ogawa Bun-ichiro Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut Imaoka Masako Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut Hayashi Shim-mo San-Ei Gen F.F.I., Inc, 1-4-9 Hirano-machi, Chuo-ku, 540-8688, Osaka, Japan aut Suzuki Kazuhiko Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut Shibutani Makoto Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut Mitsumori Kunitoshi Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut Archives of Toxicology Springer-Verlag 85/11(2011-11-01), 1475-1484 0340-5761 85:11<1475 2011 85 204 https://doi.org/10.1007/s00204-011-0696-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0696-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Morita Reiko Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Shimamoto Keisuke Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Ishii Yuji Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, 158-8501, Tokyo, Japan aut NATIONALLICENCE 700 1- Kuwata Kazunori Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Ogawa Bun-ichiro Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Imaoka Masako Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Hayashi Shim-mo San-Ei Gen F.F.I., Inc, 1-4-9 Hirano-machi, Chuo-ku, 540-8688, Osaka, Japan aut NATIONALLICENCE 700 1- Suzuki Kazuhiko Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Shibutani Makoto Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Mitsumori Kunitoshi Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, 183-8509, Tokyo, Japan aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/11(2011-11-01), 1475-1484 0340-5761 85:11<1475 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer