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Suppressive effect of enzymatically modified isoquercitrin on phenobarbital-induced liver tumor promotion in rats

  • Genotoxicity and Carcinogenicity
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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.

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Authors and Affiliations

  1. Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo, 183-8509, Japan

    Reiko Morita, Keisuke Shimamoto, Kazunori Kuwata, Bun-ichiro Ogawa, Masako Imaoka, Kazuhiko Suzuki, Makoto Shibutani & Kunitoshi Mitsumori

  2. Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan

    Keisuke Shimamoto

  3. Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan

    Yuji Ishii

  4. San-Ei Gen F.F.I., Inc, 1-4-9 Hirano-machi, Chuo-ku, Osaka, 540-8688, Japan

    Shim-mo Hayashi

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  1. Reiko Morita
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Morita, R., Shimamoto, K., Ishii, Y. et al. Suppressive effect of enzymatically modified isoquercitrin on phenobarbital-induced liver tumor promotion in rats. Arch Toxicol 85, 1475–1484 (2011). https://doi.org/10.1007/s00204-011-0696-z

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