Intestinal flora induces the expression of Cyp3a in the mouse liver

T. Toda, N. Saito, N. Ikarashi, K. Ito, M. Yamamoto, A. Ishige, Kenji Watanabe, K. Sugiyama

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

In order to determine the effects of intestinal flora on the expression of cytochrome P450 (CYP), the mRNA expression of CYP was compared between specific pathogen-free (SPF) and germ-free (GF) mice. Most of the major CYP isozymes showed higher expression in the livers of SPF mice compared with GF mice. Nuclear factors such as pregnane - receptor (PXR) and constitutive androstane receptor (CAR), as well as transporters and conjugation enzymes involved in the detoxification of lithocholic acid (LCA), also showed higher expression in SPF mice. The findings suggest that in the livers of SPF mice, LCA produced by intestinal flora increases the expression of CYPs via activation of PXR and CAR. Drugs such as antibiotics, some diseases and ageing, etc. are known to alter intestinal flora. The present findings suggest that such changes also affect CYP and are one of the factors responsible for individual differences in pharmacokinetics.

Original languageEnglish
Pages (from-to)323-334
Number of pages12
JournalXenobiotica
Volume39
Issue number4
DOIs
Publication statusPublished - 2009

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Pathogens
Specific Pathogen-Free Organisms
Liver
Cytochrome P-450 Enzyme System
Lithocholic Acid
Pregnanes
Detoxification
Pharmacokinetics
Isoenzymes
Individuality
Aging of materials
Chemical activation
Anti-Bacterial Agents
Messenger RNA
Gastrointestinal Microbiome
Enzymes
Pharmaceutical Preparations
constitutive androstane receptor

Keywords

  • Cyp3a
  • Germ-free
  • Intestinal flora
  • Lithocholic acid
  • Nuclear transcription factors
  • Pregnane X receptor (PXR)

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology
  • Biochemistry
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

Toda, T., Saito, N., Ikarashi, N., Ito, K., Yamamoto, M., Ishige, A., ... Sugiyama, K. (2009). Intestinal flora induces the expression of Cyp3a in the mouse liver. Xenobiotica, 39(4), 323-334. https://doi.org/10.1080/00498250802651984

Intestinal flora induces the expression of Cyp3a in the mouse liver. / Toda, T.; Saito, N.; Ikarashi, N.; Ito, K.; Yamamoto, M.; Ishige, A.; Watanabe, Kenji; Sugiyama, K.

In: Xenobiotica, Vol. 39, No. 4, 2009, p. 323-334.

Research output: Contribution to journalArticle

Toda, T, Saito, N, Ikarashi, N, Ito, K, Yamamoto, M, Ishige, A, Watanabe, K & Sugiyama, K 2009, 'Intestinal flora induces the expression of Cyp3a in the mouse liver', Xenobiotica, vol. 39, no. 4, pp. 323-334. https://doi.org/10.1080/00498250802651984
Toda T, Saito N, Ikarashi N, Ito K, Yamamoto M, Ishige A et al. Intestinal flora induces the expression of Cyp3a in the mouse liver. Xenobiotica. 2009;39(4):323-334. https://doi.org/10.1080/00498250802651984
Toda, T. ; Saito, N. ; Ikarashi, N. ; Ito, K. ; Yamamoto, M. ; Ishige, A. ; Watanabe, Kenji ; Sugiyama, K. / Intestinal flora induces the expression of Cyp3a in the mouse liver. In: Xenobiotica. 2009 ; Vol. 39, No. 4. pp. 323-334.
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