Next Article in Journal
Interaction of Classical Platinum Agents with the Monomeric and Dimeric Atox1 Proteins: A Molecular Dynamics Simulation Study
Next Article in Special Issue
Towards Automated Binding Affinity Prediction Using an Iterative Linear Interaction Energy Approach
Previous Article in Journal
Efficacy and Feasibility of the Epithelial Cell Adhesion Molecule (EpCAM) Immunomagnetic Cell Sorter for Studies of DNA Methylation in Colorectal Cancer
Previous Article in Special Issue
CYP 2D6 Binding Affinity Predictions Using Multiple Ligand and Protein Conformations
Open AccessArticle

Chimeric Mice with Humanized Livers: A Unique Tool for in Vivo and in Vitro Enzyme Induction Studies

1
PhoenixBio Co., Ltd., 3-4-1, Kagamiyama, Higashihiroshima, Hiroshima 739-0046, Japan
2
Liver Research Project Center, Hiroshima University, 1-2-3 Kasumi, Minami, Hiroshima, Hiroshima 734-8551, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2014, 15(1), 58-74; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms15010058
Received: 1 November 2013 / Revised: 5 December 2013 / Accepted: 6 December 2013 / Published: 20 December 2013
(This article belongs to the Special Issue Xenobiotic Metabolism)
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. View Full-Text
Keywords: liver; P450 induction; humanized animal model; rifampicin; 3-methylcholanthrene liver; P450 induction; humanized animal model; rifampicin; 3-methylcholanthrene
Show Figures

MDPI and ACS Style

Kakuni, M.; Yamasaki, C.; Tachibana, A.; Yoshizane, Y.; Ishida, Y.; Tateno, C. Chimeric Mice with Humanized Livers: A Unique Tool for in Vivo and in Vitro Enzyme Induction Studies. Int. J. Mol. Sci. 2014, 15, 58-74. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms15010058

AMA Style

Kakuni M, Yamasaki C, Tachibana A, Yoshizane Y, Ishida Y, Tateno C. Chimeric Mice with Humanized Livers: A Unique Tool for in Vivo and in Vitro Enzyme Induction Studies. International Journal of Molecular Sciences. 2014; 15(1):58-74. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms15010058

Chicago/Turabian Style

Kakuni, Masakazu; Yamasaki, Chihiro; Tachibana, Asato; Yoshizane, Yasumi; Ishida, Yuji; Tateno, Chise. 2014. "Chimeric Mice with Humanized Livers: A Unique Tool for in Vivo and in Vitro Enzyme Induction Studies" Int. J. Mol. Sci. 15, no. 1: 58-74. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms15010058

Find Other Styles

Article Access Map by Country/Region

1
Only visits after 24 November 2015 are recorded.
Search more from Scilit
 
Search
Back to TopTop