Novel bioactivation pathway of benzbromarone mediated by cytochrome P450

Yumina Kitagawara, Tomoyuki Ohe, Kumiko Tachibana, Kyoko Takahashi, Shigeo Nakamura, Tadahiko Mashino

研究成果: Article査読

10 被引用数 (Scopus)

抄録

Benzbromarone (BBR) is a hepatotoxic drug, but the detailed mechanism of its toxicity remains unknown. We identified 2,6-dibromohydroquinone (DBH) and mono-debrominated catechol (2-ethyl-3-(3-bromo-4,5-dihydroxybenzoyl) benzofuran; CAT) as novel metabolites of BBR in rat and human liver microsomal systems by comparison with chemically synthesized authentic compounds, and we also elucidated that DBH is formed by cytochrome P450 2C9 and that CAT is formed mainly by CYP1A1, 2D6, 2E1, and 3A4. Furthermore, CAT, DBH, and the oxidized form of DBH are highly cytotoxic in HepG2 compared with BBR. Taken together, our data demonstrate that DBH, a novel reactive metabolite, may be relevant to BBR-induced hepatotoxicity.

本文言語English
ページ(範囲)1303-1306
ページ数4
ジャーナルDrug Metabolism and Disposition
43
9
DOI
出版ステータスPublished - 2015 9 1

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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