کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8993097 | 1113458 | 2005 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Induction of Human CYP1A2 and CYP3A4 in Primary Culture of Hepatocytes from Chimeric Mice with Humanized Liver
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Chimeric mice with near-completely humanized liver were constructed by transplantating hepatocytes from a Japanese and Caucasian donor. In the present study, we investigated the induction of human CYP1A2 and CYP3A4 mRNA in a primary culture of the cryopreserved chimeric mouse hepatocytes. β-naphthoflavone (β-NF) and rifampicin (Rif) were used as typical cytochrome P450 (CYP) inducers for CYP1A2 and CYP3A4, respectively. Analysis was performed by the real-time reverse-transcription polymerase chain reaction method. CYP1A2 mRNA in the primary culture of chimeric mouse hepatocytes in mice No. 1, 2, and 3 was significantly increased 3.8-, 6.3-, and 3.3-fold by 5 μΠβ-NF exposure, respectively, compared with the 0.1% DMSO treated control (p< 0.01). CYP3A4 mRNA in the primary culture of chimeric mouse hepatocytes in mice No. 1, 2, and 3 was significantly increased 8.4-fold (p< 0.001), 2.2-fold (p< 0.01), and 2.3-fold (p< 0.05) by 50 μΠRif exposure, respectively, compared with the 0.1% DMSO treated control. The present study demonstrated that a primary culture of cryopreserved hepatocytes from chimeric mice with humanized liver could be used for evaluating the induction of drug metabolizing enzymes in human. This in vitro method may be a useful method for screening the induction potency of new drug candidates on drug metabolizing enzymes.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Drug Metabolism and Pharmacokinetics - Volume 20, Issue 2, 2005, Pages 121-126
Journal: Drug Metabolism and Pharmacokinetics - Volume 20, Issue 2, 2005, Pages 121-126
نویسندگان
Masuhiro Nishimura, Tsuyoshi Yokoi, Chise Tateno, Miho Kataoka, Eiji Takahashi, Toru Horie, Katsutoshi Yoshizato, Shinsaku Naito,