Enhanced liver tumor promotion but not liver initiation activity in rats subjected to combined administration of omeprazole and β-naphthoflavone
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- Hayashi Hitomi
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology United Graduate School of Veterinary Science, Gifu University
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- Taniai Eriko
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology United Graduate School of Veterinary Science, Gifu University
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- Morita Reiko
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology United Graduate School of Veterinary Science, Gifu University
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- Hayashi Masahiro
- Gotemba Laboratory, Bozo Research Center Inc.
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- Nakamura Daichi
- Gotemba Laboratory, Bozo Research Center Inc.
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- Wakita Atsushi
- Gotemba Laboratory, Bozo Research Center Inc.
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- Suzuki Kazuhiko
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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- Shibutani Makoto
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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- Mitsumori Kunitoshi
- Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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抄録
Omeprazole (OPZ) and β-naphthoflavone (BNF) are cytochrome P450 (CYP)1A inducers and have liver tumor promoting effects. In this study, we investigated the co-promoting and co-initiating effects of OPZ and BNF in rats. In Experiment 1, male rats were subjected to partial hepatectomy (PH), and given oral doses of 138 or 276 mg/kg OPZ, 0.125% or 0.25% BNF or 138 mg/kg OPZ+0.125% BNF (n = 9~12) for 6 weeks after N-diethylnitrosamine (DEN) initiation. In Experiment 2, male rats were treated with oral doses of 138 or 276 mg/kg OPZ, 0.03% or 0.06% BNF or 138 mg/kg OPZ+0.03% BNF (n = 11~12) for 9 days starting 1 week before initiating treatment. As an initiating treatment, 2-Amino-3,4-dimethylimidazo[4,5-f]quinolone (MeIQx) was orally administered 12 hr after PH. The rats were fed a basal diet for 15 days, followed by a diet containing 0.015% 2-acetylaminofluorene for the next 10 days with a single oral dose of carbon tetrachloride. In Experiment 1, the number and area of glutathione S-transferase placental form-positive foci in the OPZ+BNF group were significantly higher than the average values of the High OPZ or the High BNF group. The expression of cyclooxygenase-2 (Cox-2) and COX-2 protein in the liver significantly increased in the OPZ+BNF group. In Experiment 2, liver initiation activity was not enhanced by the co-administration of OPZ+BNF. The results of our studies suggest that the co-administration of OPZ and BNF results in synergistic effects in the liver tumor promotion probably owing to increased COX-2 expression, but no modifying effect in the liver initiation activity of MeIQx in rats.
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 37 (5), 969-985, 2012
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390282679882383104
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- NII論文ID
- 130004447009
- 10030876438
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- NII書誌ID
- AN00002808
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- COI
- 1:STN:280:DC%2BC3s%2Fis1Ontw%3D%3D
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 024030331
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- PubMed
- 23038005
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可