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首页> 外文期刊>Journal of biochemical and molecular toxicology >In vitro In vitro and in vivo in vivo metabolic activation of berbamine to quinone methide intermediate
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In vitro In vitro and in vivo in vivo metabolic activation of berbamine to quinone methide intermediate

机译:体外体外和体内体内的体内代谢活化Berbamine以醌甲基中间体

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摘要

Abstract Berbamine (BBM) is a bisbenzylisoquinoline alkaloid isolated from herbal medicine Berberis amurensis . BBM has been widely used for the treatment of leukemia. Recent studies demonstrated that exposure to BBM can give rise to cytotoxicity. The major objective of this study was to explore the metabolic activation of BBM in vitro and in vivo . Two oxidative metabolites (M1 and M2) and an N ‐acetylcysteine (NAC) conjugate (M3) were detected in human liver microsomal incubations of BBM supplemented with NAC, and the formation of all metabolites was NADPH dependent. Microsomal inhibition and recombinant P450 enzyme incubation studies demonstrated that P450 3A4 was the major enzyme responsible for the metabolic activation of BBM. In addition, a BBM–cysteine conjugate (M4) was detected in the urine of rats given BBM. The metabolism study will facilitate the understanding of the biochemical mechanisms of BBM‐induced cytotoxicity.
机译:摘要小檗胺(BBM)是从中药小檗中分离得到的一种双苄基异喹啉生物碱。BBM已被广泛用于治疗白血病。最近的研究表明,暴露于BBM可引起细胞毒性。本研究的主要目的是探索BBM在体外和体内的代谢活化。在补充了NAC的BBM的人肝微粒体培养中检测到两种氧化代谢物(M1和M2)和一种N-乙酰半胱氨酸(NAC)结合物(M3),并且所有代谢物的形成都依赖于NADPH。微粒体抑制和重组P450酶培养研究表明,P450 3A4是BBM代谢激活的主要酶。此外,在给予BBM的大鼠尿液中检测到BBM-半胱氨酸结合物(M4)。代谢研究将有助于理解BBM诱导的细胞毒性的生化机制。

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  • 来源
  • 作者单位

    School of PharmacyShenyang Pharmaceutical UniversityShenyang Liaoning 110016 People's Republic of;

    School of PharmacyShenyang Pharmaceutical UniversityShenyang Liaoning 110016 People's Republic of;

    School of PharmacyShenyang Pharmaceutical UniversityShenyang Liaoning 110016 People's Republic of;

    School of PharmacyShenyang Pharmaceutical UniversityShenyang Liaoning 110016 People's Republic of;

    Key Laboratory of Structure‐Based Drug Design &

    Discovery of Ministry of EducationShenyang;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

    berbamine; metabolic activation; quinone methide;

    机译:Berbamine;代谢激活;醌美氨基;

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