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首页> 外文期刊>薬物動態 >A metabolism-based approach to elucidating the mechanism of liver dysfunctiion induced by troglitazone polymorphism of UGTs?
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A metabolism-based approach to elucidating the mechanism of liver dysfunctiion induced by troglitazone polymorphism of UGTs?

机译：一种基于代谢的方法来阐明UGTs诱导的Troglitazone多态性诱导的肝功能障碍机制？

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摘要

We investigated whether or not the liver dysfunction in patients reated with troglitazone(TG)is related to polymorphism in UDP-glucuronosyltransferases(UGTs),which are partially responsible for TG metabolism.In the toxicological sttudy of TG using gunn rats,which are hereditarily deficient in the UGT1 family,the metabolic profile of TG in Gunnn rats was very similar to that of Wistar rats,the parent strain of Gunn rats,and no sign of the liver dysfunction was observed in both rats.UGTs involved in TG glucuronidation in rats and humans have been characterized.The experiments using liver microsomes of Gunnr ats suggested that the enzyme responsible for glucuronidation in rats was UGT2B2,and androsterone UGT,by inhibition studies.In humans,contribution of UGT1A1 was estimated to be about 30 precent of the total TG alucuronidation by UGTs,using human liver microsomes and recombinant UGTs.Other UGT1 and UGT2 enzymes seem to be responsible for the remaining 70 precent of TG glucuronidation.The multiplicity of UGTs involved in TG glucuronidation in humans may even allow patients lacking bilirubin UGT(UGT1A1)activity to metabolized TG to the glucuronide.These observations suggest that the polymorphism of UGT is not the reason for the liver dysfunction induced by teh TG observations suggest that the polymorphism of UGT is not the reason for the liver dysfunction induced by the TG treatment.
机译：我们调查了用Troglitazone（Tg）加油的患者的肝功能障碍是否与UDP-葡糖醛糖基糖基转移酶（UGTS）中的多态性有关，其部分原因是Tg代谢。使用Gunn大鼠的Tg的毒理学Study，它们缺陷缺陷在UGT1家族中，Gunnn大鼠TG的代谢谱与Wistar大鼠的TG，枪血清大鼠的亲本菌株，并且在大鼠中涉及TG葡萄糖醛化的大鼠中没有观察到肝功能障碍的迹象。已经表征了人类的实验。使用GunnR ATS的肝脏微粒体的实验表明，负责大鼠葡萄糖醛酸化的酶是UGT2B2，并且通过抑制研究androsternoneugt。在人类中，估计UGT1A1的贡献是总TG的约30个预约使用人肝微粒体和重组UGTS的UGTS通过UGT核化。其他UGT1和UGT2酶似乎是TG葡萄糖醛酸的剩余70份的负责.T他在人类中涉及TG葡萄糖醛化的多种UGT可以让患者缺乏胆红素UGT（UGT1A1）的患者将TG代谢到葡糖醛醛。这意味着UGT的多态性不是TG观察结果所诱导的肝功能障碍的原因UGT的多态性不是TG处理诱导肝功能障碍的原因。

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  • 来源
    《薬物動態》 |2001年第suppla期|共2页
  • 作者

    Yasushi Yoshigae; Toshiyuki Watanabe; Kumiko Koyama; Wataru Takasaki; Sunao Manabe; Toshihiko Ikeda;

  • 作者单位

    Pharmacokinetics and Drug Delivery Research Laboratories Sankyo Co. Ltd. 2-58 Hiromachi 1-chome Shinagawa-ku 140-8710 Japan;

    Medicanal Safety Research Laboratories Sankyo Co. Ltd. 717 Horikoshi Fukurio Shizuoka 437-0065 Japan;

    Pharmacokinetics and Drug Delivery Research Laboratories Sankyo Co. Ltd. 2-58 Hiromachi 1-chome Shinagawa-ku 140-8710 Japan;

    Pharmacokinetics and Drug Delivery Research Laboratories Sankyo Co. Ltd. 2-58 Hiromachi 1-chome Shinagawa-ku 140-8710 Japan;

    Medicanal Safety Research Laboratories Sankyo Co. Ltd. 717 Horikoshi Fukurio Shizuoka 437-0065 Japan;

    Pharmacokinetics and Drug Delivery Research Laboratories Sankyo Co. Ltd. 2-58 Hiromachi 1-chome Shinagawa-ku 140-8710 Japan;

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  • 正文语种 jpn
  • 中图分类 药学;制药化学工业;
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