著者

御園生 一 石川 雅之 和田 和千 Hajime Misonou Masayuki Ishikawa Kazuyuki Wada

雑誌

【C】電子・情報・システム部門 電子回路研究会

巻号頁・発行日

2011-03-24

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正弦波の歪み率は増幅器などの歪み率測定における測定限界を決定している。そのため低歪みな正弦波が要求されている。一般に、発振回路の出力が目的の振幅となったとき、発振条件を臨界状態にすることにより低歪み化することができるとされている。そこで本研究では制御回路の発振出力を多相整流する部分に着目し、整流法を改善することにより正弦波の低歪み化を目指す。

著者

Kaoru KOBAYASHI Eri KAJIWARA Masayuki ISHIKAWA Hanaka MIMURA Hidenobu OKA Yoko EJIRI Masaya HOSODA Kan CHIBA

出版者

日本薬物動態学会 会長/日本薬物動態学会 DMPK編集委員長

雑誌

Drug Metabolism and Pharmacokinetics (ISSN:13474367)

巻号頁・発行日

vol.28, no.3, pp.265-268, 2013 (Released:2013-06-25)

参考文献数

18

被引用文献数

14

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Treatment with benzbromarone (BBR), a potent uricosuric drug, can be associated with liver injury. Recently, we reported that culture of human hepatocellular carcinoma FLC-4 cells on micro-space cell culture plates could increase the functional expression of drug-metabolizing enzymes including CYP3A4 and CYP2C9, which are involved in 1′-hydroxylation and 6-hydroxylation of BBR, respectively. Therefore, we examined whether BBR and its two metabolites (1′-hydroxy BBR and 6-hydroxy BBR) have cytotoxic effects in FLC4 cells cultured on micro-space cell culture plates. The present study showed that BBR and 1′-hydroxy BBR, but not 6-hydroxy BBR, have cytotoxic effects in cells cultured on micro-space cell culture plates. BBR-induced cytotoxicity was decreased by CYP3A inhibitors (itraconazole and ketoconazole), an Nrf2 activator (tert-butylhydroquinone) and a GSH precursor (N-acetyl-L-cystein). In contrast, BBR-induced cytotoxicity was increased by a GSH biosynthesis inhibitor (buthionine sulfoximine) and an inhibitor of NAD(P)H quinone oxidoreductase 1 (dicoumarol). These results suggested that metabolic activation of 1′-hydroxy BBR via CYP3A, formation of quinone metabolites and the decrease in GSH levels were involved in the BBR-induced cytotoxicity observed in FLC4 cells cultured on micro-space cell culture plates.