title: Orange juice and its component, hesperidin, decrease the expression of multidrug resistance-associated protein 2 in rat small intestine and liver.
abstract: We investigated the effects of orange juice (OJ) or hesperidin, a component of OJ, on the pharmacokinetics of pravastatin (PRV) and the expression of both protein and mRNA of multidrug resistance-associated protein 2 (Mrp2) in the rat small intestine and liver. Eight-week-old male Sprague-Dawley rats were used in this study. OJ or a 0.079% hesperidin suspension was administered orally for 2 days. Tap water was given as a control. A single dose of PRV at 100  mg/kg p.o. was administered after 2 days of OJ, hesperidin, or tap water ingestion. The AUC, C(max), and t(1/2) values of PRV were significantly increased in OJ group. Mrp2 protein and mRNA levels in the small intestine and liver, respectively, were significantly decreased after the ingestion of OJ. The same results were obtained with hesperidin. These results suggest that the changes in PRV pharmacokinetic parameters and the decrease in Mrp2 expression caused by OJ are due to hesperidin in the juice.
authors.affiliation: Department of Pharmacology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-Ku, Kawasaki, Kanagawa 216-8511, Japan. m4wata@marianna-u.ac.jp
authors.forename: Minoru
authors.initials: M
authors.lastname: Watanabe
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takeba
authors.forename: Toshio
authors.initials: T
authors.lastname: Kumai
authors.forename: Masami
authors.initials: M
authors.lastname: Tanaka
authors.forename: Shinobu
authors.initials: S
authors.lastname: Tatsunami
authors.forename: Sachiko
authors.initials: S
authors.lastname: Takenoshita-Nakaya
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Harimoto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001628:Beverages; D032084:Citrus sinensis / Q000737:chemistry*; D004334:Drug Administration Schedule; D006569:Hesperidin / Q000494:pharmacology*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000187:drug effects / Q000378:metabolism*; D010949:Plasma / Q000187:drug effects / Q000378:metabolism; D017035:Pravastatin / Q000097:blood / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006569:Hesperidin; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017035:Pravastatin; D012333:RNA, Messenger