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Induction of hepatic CYP3A4 expression by cholesterol and cholic acid: Alterations of gene expression, microsomal activity, and pharmacokinetics.

التفاصيل البيبلوغرافية
العنوان: Induction of hepatic CYP3A4 expression by cholesterol and cholic acid: Alterations of gene expression, microsomal activity, and pharmacokinetics.
المؤلفون: Minegishi G; Department of Biopharmaceutics, Graduate School of Clinical Pharmacy, Meiji Pharmaceutical University, Kiyose, Japan., Kobayashi Y; Department of Biopharmaceutics, Graduate School of Clinical Pharmacy, Meiji Pharmaceutical University, Kiyose, Japan., Fujikura M; Department of Biopharmaceutics, Graduate School of Clinical Pharmacy, Meiji Pharmaceutical University, Kiyose, Japan., Sano A; Department of Biopharmaceutics, Graduate School of Clinical Pharmacy, Meiji Pharmaceutical University, Kiyose, Japan., Kazuki Y; Chromosome Engineering Research Center (CERC), Tottori University, Tottori, Japan.; Department of Chromosome Biomedical Engineering, Faculty of Medicine, School of Life Science, Tottori University, Tottori, Japan., Kobayashi K; Department of Biopharmaceutics, Graduate School of Clinical Pharmacy, Meiji Pharmaceutical University, Kiyose, Japan.
المصدر: Pharmacology research & perspectives [Pharmacol Res Perspect] 2024 Jun; Vol. 12 (3), pp. e1197.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics Country of Publication: United States NLM ID: 101626369 Publication Model: Print Cited Medium: Internet ISSN: 2052-1707 (Electronic) Linking ISSN: 20521707 NLM ISO Abbreviation: Pharmacol Res Perspect Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Hoboken, NJ] : John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics, [2013]-
مواضيع طبية MeSH: Cholic Acid*/metabolism , Cytochrome P-450 CYP3A*/metabolism , Cytochrome P-450 CYP3A*/genetics , Microsomes, Liver*/metabolism , Cholesterol*/metabolism , Cholesterol*/blood , Liver*/metabolism , Liver*/drug effects , Triazolam*/pharmacokinetics , Triazolam*/metabolism, Animals ; Mice ; Male ; Humans ; Mice, Transgenic ; Hydroxylation
مستخلص: Human cytochrome P450 3A4 (CYP3A4) is a drug-metabolizing enzyme that is abundantly expressed in the liver and intestine. It is an important issue whether compounds of interest affect the expression of CYP3A4 because more than 30% of commercially available drugs are metabolized by CYP3A4. In this study, we examined the effects of cholesterol and cholic acid on the expression level and activity of CYP3A4 in hCYP3A mice that have a human CYP3A gene cluster and show human-like regulation of the coding genes. A normal diet (ND, CE-2), CE-2 with 1% cholesterol and 0.5% cholic acid (HCD) or CE-2 with 0.5% cholic acid was given to the mice. The plasma concentrations of cholesterol, cholic acid and its metabolites in HCD mice were higher than those in ND mice. In this condition, the expression levels of hepatic CYP3A4 and the hydroxylation activities of triazolam, a typical CYP3A4 substrate, in liver microsomes of HCD mice were higher than those in liver microsomes of ND mice. Furthermore, plasma concentrations of triazolam in HCD mice were lower than those in ND mice. In conclusion, our study suggested that hepatic CYP3A4 expression and activity are influenced by the combination of cholesterol and cholic acid in vivo.
(© 2024 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)
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معلومات مُعتمدة: JPMJCR18S4 Japan Science and Technology Agency; JP23ama121046 Japan Agency for Medical Research and Development; 23K06242 Japan Society for the Promotion of Science
فهرسة مساهمة: Keywords: cholesterol; cholic acids; cytochrome P‐450 CYP3A; enzyme induction; metabolism; pharmacokinetics
المشرفين على المادة: G1JO7801AE (Cholic Acid)
EC 1.14.14.1 (Cytochrome P-450 CYP3A)
97C5T2UQ7J (Cholesterol)
1HM943223R (Triazolam)
تواريخ الأحداث: Date Created: 20240422 Date Completed: 20240423 Latest Revision: 20240507
رمز التحديث: 20240507
مُعرف محوري في PubMed: PMC11033495
DOI: 10.1002/prp2.1197
PMID: 38644590
قاعدة البيانات: MEDLINE
الوصف
تدمد:2052-1707
DOI:10.1002/prp2.1197