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| Content Provider | MDPI |
|---|---|
| Author | Kakuni, Masakazu Yamasaki, Chihiro Tachibana, Asato Yoshizane, Yasumi Ishida, Yuji Tateno, Chise |
| Abstract | We performed in vivo and in vitro studies to determine the induction of human cytochrome P450 (CYP) using chimeric mice with humanized liver (PXB-mice®) and human hepatocytes isolated from the PXB-mice (PXB-cells), which were derived from the same donor. For the in vivo study, PXB-mice were injected with 3-methylcholanthrene (3-MC, 2 or 20 mg/kg) or rifampicin (0.1 or 10 mg/kg) for four days. For the in vitro study, PXB-cells were incubated with 3-MC (10, 50, or 250 ng/mL) or with rifampicin (5 or 25 μg/mL). The CYP1A1 and 1A2, and CYP3A4 mRNA expression levels increased significantly in the PXB-mouse livers with 20 mg/kg of 3-MC (Cmax, 12.2 ng/mL), and 10 mg/kg rifampicin (Cmax, 6.9 µg/mL), respectively. The CYP1A1 mRNA expression level increased significantly in PXB-cells with 250 ng/mL of 3-MC, indicating lower sensitivity than in vivo. The CYP1A2 and CYP3A4 mRNA expression levels increased significantly with 50 ng/mL of 3-MC, and 5 μg/mL of rifampicin, respectively, which indicated that the sensitivities were similar between in vivo and in vitro studies. In conclusion, PXB-mice and PXB-cells provide a robust model as an intermediate between in vivo and in vitro human metabolic enzyme induction studies. |
| File Size | 620544 |
| Ending Page | 74 |
| Page Count | 17 |
| Starting Page | 58 |
| File Format | |
| e-ISSN | 14220067 |
| DOI | 10.3390/ijms15010058 |
| Journal | International Journal of Molecular Sciences |
| Issue Number | 1 |
| Volume Number | 15 |
| Language | English |
| Publisher Date | 2013-12-20 |
| Access Restriction | Open |
| Subject Keyword | liver P450 induction humanized animal model rifampicin 3-methylcholanthrene |
| Content Type | Text |
| Resource Type | Article |
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