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

Fühner-Wieland's Sammlung von Vergiftungsfällen - Tập 85 - Trang 1475-1484 - 2011
Reiko Morita1, Keisuke Shimamoto1,2, Yuji Ishii3, Kazunori Kuwata1, Bun-ichiro Ogawa1, Masako Imaoka1, Shim-mo Hayashi4, Kazuhiko Suzuki1, Makoto Shibutani1, Kunitoshi Mitsumori1
1Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Tokyo, Japan
2Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, Gifu, Japan
3Division of Pathology, National Institute of Health Sciences, Tokyo, Japan
4San-Ei Gen F.F.I., Inc., Osaka, Japan

Tóm tắt

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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