title: Inhibitory effects of kale ingestion on metabolism by cytochrome P450 enzymes in rats.
abstract: Kale (Brassica oleracea L. var acephala DC) is a leafy green vegetable belonging to the cabbage family (Brassicaceae) that contains a large amount of health-promoting phytochemicals. There are any reports about the effects of kale ingestion on the chemoprevention function and mechanism, but the interactions between kale and drugs have not been researched. We investigated the effects of kale intake on cytochrome P450 (CYP) metabolism by using cocktail probe drugs, including midazolam (for CYP3A4), caffeine (for CYP1A2), dextromethorphan (for CYP2D6), tolbutamide (for CYP2C9), omeprazole (for CYP2C19), and chlorzoxazone (for CYP2E1). Cocktail drugs were administered into rats treated with kale and cabbage (2000 mg/kg) for a week. The results showed that kale intake induced a significant increase in plasma levels and the AUC of midazolam, caffeine, and dextromethorphan. In addition, the plasma concentration and AUC of omeprazole tended to increase. Additionally, no almost differences in the mRNA expression levels of CYP enzymes in the liver were observed. In conclusion, kale ingestion was considered to have an inhibitory effect on the activities of CYP3A4, 1A2, 2D6, and 2C19 for a reason competitive inhibition than inhibitory changes in the mRNA expressions.
authors.affiliation: Research Institute, FANCL Co., Kamishinano, Totsuka-ku, Yokohama, Japan. izumi0609@fancl.co.jp
authors.forename: Izumi
authors.initials: I
authors.lastname: Yamasaki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yamada
authors.forename: Nobuo
authors.initials: N
authors.lastname: Uotsu
authors.forename: Sachiyuki
authors.initials: S
authors.lastname: Teramoto
authors.forename: Risa
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001937:Brassica / Q000378:metabolism*; D002110:Caffeine / Q000493:pharmacokinetics; D002753:Chlorzoxazone / Q000493:pharmacokinetics; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D003580:Cytochromes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003915:Dextromethorphan / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D008099:Liver / Q000201:enzymology; D008657:Metabolic Clearance Rate; D008874:Midazolam / Q000493:pharmacokinetics*; D009853:Omeprazole / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014044:Tolbutamide / Q000493:pharmacokinetics
chemical_list: D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D003580:Cytochromes; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D002110:Caffeine; D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System; D014044:Tolbutamide; D019392:Cytochrome P-450 CYP2E1; C507848:CYP2C9 protein, rat; C017170:Cyp1a2 protein, rat; C465260:Cyp3a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D002753:Chlorzoxazone; D009853:Omeprazole; D008874:Midazolam