Effects of β-Naphthoflavone on Ugt1a6 and Ugt1a7 Expression in Rat Brain

DOI Web Site Web Site PubMed 被引用文献2件 参考文献37件
  • Sakakibara Yukiko
    Department of Pharmaceutics, Faculty of Pharmacy, Meijo University
  • Katoh Miki
    Department of Pharmaceutics, Faculty of Pharmacy, Meijo University
  • Kondo Yuya
    Department of Pharmaceutics, Faculty of Pharmacy, Meijo University
  • Nadai Masayuki
    Department of Pharmaceutics, Faculty of Pharmacy, Meijo University

この論文をさがす

説明

Uridine 5′-diphosphate-glucuronosyltransferase (UGT) catalyzes a major phase II reaction in a drug-metabolizing enzyme system. Although the UGT1A subfamily is expressed mainly in the liver, it is also expressed in the brain. The purpose of the present study was to elucidate the effect of β-naphthoflavone (BNF), one of the major inducers of drug-metabolizing enzymes, on Ugt1a6 and Ugt1a7 mRNA expression and their glucuronidation in the rat brain. Eight-week-old male Sprague-Dawley rats were treated intraperitoneally with BNF (80 mg/kg), once daily for 7 d. Ugt1a6 and Ugt1a7 mRNA expression increased in the cerebellum and hippocampus (Ugt1a6: 2.1- and 2.3-fold, respectively; Ugt1a7: 1.7- and 2.8-fold, respectively); acetaminophen glucuronidation also increased in the same regions by 4.1- and 2.7-fold, respectively. BNF induced Ugt1a6 and Ugt1a7 mRNA expression and their glucuronidation, and the degree of induction differed among 9 regions. BNF also upregulated CYP1A1, CYP1A2, and CYP1B1 mRNAs in the rat brain. Since the aryl hydrocarbon receptor signaling pathway was activated by BNF, it is indicated that Ugt1a6 and Ugt1a7 were induced via AhR in the rat brain. This study clarified that Ugt1a6 and Ugt1a7 mRNA expression and their enzyme activities were altered by BNF, suggesting that these changes may lead to alteration in the pharmacokinetics of UGT substrate in rat brain.

収録刊行物

被引用文献 (2)*注記

もっと見る

参考文献 (37)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ