title: High-dose green tea polyphenol intake decreases CYP3A expression in a liver-specific manner with increases in blood substrate drug concentrations.
abstract: In recent years, the intake of functional foods containing high-doses of green tea polyphenols (GP) has been increasing. In this study, the long-term safety of high-dose GP was assessed from a pharmacokinetic point of view by focusing on the drug-metabolizing enzyme, cytochrome P450 (CYP). Mice were fed a diet containing 3% GP for 4weeks, and the CYP expression levels and activity were determined. The GP-treated group showed a significant decrease in the hepatic CYP3A and an increase in the hepatic CYP2C expression compared with the control group. CYP1A, CYP2D, and CYP2E expression were not different between the GP-treated and the control groups. In the small intestine, there were no differences in the CYP3A protein levels between the groups. The increase in the plasma triazolam concentration in the GP-treated group was observed. Although no changes were found in the hepatic CYP3A levels in mice receiving a diet containing 0.1% GP for 4weeks, a significant decrease was seen in the hepatic CYP3A level in mice receiving a diet containing 3% GP for only 1week. This study revealed that the intake of a high-dose GP results in a liver-specific decrease in the CYP3A expression level. The results also indicated that the effects of GP on CYP3A were not observed following the intake of a low-dose GP. In the future, caution should be taken in cases when functional foods containing a high-dose GP are concomitantly consumed with a CYP3A substrate drug.
authors.affiliation: Department of Clinical Pharmacokinetics, Hoshi University, Japan.
authors.forename: Nobutomo
authors.initials: N
authors.lastname: Ikarashi
authors.affiliation: Department of Clinical Pharmacokinetics, Hoshi University, Japan.
authors.forename: Sosuke
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Clinical Pharmacokinetics, Hoshi University, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Hirobe
authors.affiliation: Department of Clinical Pharmacokinetics, Hoshi University, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kusunoki
authors.affiliation: Department of Clinical Pharmacokinetics, Hoshi University, Japan.
authors.forename: Risako
authors.initials: R
authors.lastname: Kon
authors.affiliation: Department of Clinical Pharmacokinetics, Hoshi University, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ochiai
authors.affiliation: Department of Clinical Pharmacokinetics, Hoshi University, Japan. Electronic address: sugiyama@hoshi.ac.jp.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D059808:Polyphenols / Q000008:administration & dosage* / Q000009:adverse effects*; D013662:Tea / Q000009:adverse effects*; D014229:Triazolam / Q000097:blood / Q000494:pharmacology; D008565:Membrane Proteins
chemical_list: D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D059808:Polyphenols; D013662:Tea; D014229:Triazolam; C496508:Cyp3a11 protein, mouse; D008565:Membrane Proteins
keywords: Cytochrome P450; Green tea polyphenol; Liver; Small intestine