Gastrectomy Increases the Expression of Hepatic Cytochrome P450 3A by Increasing Lithocholic Acid-Producing Enteric Bacteria in Mice
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- Ishii Makoto
- Department of Clinical Pharmacokinetics, Hoshi University
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- Toda Takahiro
- Department of Clinical Pharmacokinetics, Hoshi University
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- Ikarashi Nobutomo
- Department of Clinical Pharmacokinetics, Hoshi University
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- Kusunoki Yoshiki
- Department of Clinical Pharmacokinetics, Hoshi University
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- Kon Risako
- Department of Clinical Pharmacokinetics, Hoshi University
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- Ochiai Wataru
- Department of Clinical Pharmacokinetics, Hoshi University
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- Machida Yoshiaki
- Division of Applied Pharmaceutical Education and Research, Hoshi University
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- Sugiyama Kiyoshi
- Department of Clinical Pharmacokinetics, Hoshi University
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We had previously revealed that drug metabolism, as well as the expression level of hepatic CYP3A, a drug-metabolizing enzyme, increase 12 weeks after gastrectomy in mice. In this study, we elucidated the mechanism of the increased CYP3A expression. The levels of lithocholic acid (LCA)-producing bacteria (Bacteroides fragilis) and LCA in the colon did not show a significant increase up to 4 weeks after gastrectomy compared to the sham operation group. In contrast, at 12 and 24 weeks post-gastrectomy, the levels of Bacteroides fragilis and LCA were significantly higher in the gastrectomy group than in the sham operation group. At 12 and 24 weeks after gastrectomy, the hepatic nuclear translocation of pregnane X receptor (PXR) had also increased. The hepatic CYP3A11 mRNA expression and nuclear translocation of PXR after intraperitoneal administration of LCA to normal mice was significantly higher than those of the control group. The intraperitoneal administration of taurolithocholic acid (TLCA), a taurine conjugate of LCA, caused no change in the expression level of CYP3A11. We suggest that the increase in the expression level of CYP3A after gastrectomy is caused by an increase in the nuclear translocation of PXR, which is triggered by an increase in LCA-producing bacteria.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 37 (2), 298-305, 2014
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204633713152
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- NII論文ID
- 130003382122
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC2c7pvVaisQ%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 025172910
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- PubMed
- 24270587
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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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