scholarly journals Relationship between low midazolam metabolism by cytochrome P450 3A in mice and the high incidence of birth defects

2018 ◽  
Vol 43 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Satoshi Kitaoka ◽  
Jo Hatogai ◽  
Ryuki Iimura ◽  
Yuka Yamamoto ◽  
Konomi Oba ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Birth Defects ◽  
Cytochrome P450 3A ◽  
High Incidence ◽  
Midazolam Metabolism

Human cytochrome P450 3A (CYP3A) mediated midazolam metabolism

1998 ◽  
Vol 8 (2) ◽  
pp. 137???156
Author(s):  
Jukka M??enp???? ◽  
Stephen D. Hall ◽  
Barbara J. Ring ◽  
Stephen C. Strom ◽  
Steven A. Wrighton
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 3A ◽  
Human Cytochrome ◽  
Midazolam Metabolism

scholarly journals Midazolam Metabolism in Cytochrome P450 3A Knockout Mice Can Be Attributed to Up-Regulated CYP2C Enzymes

2007 ◽  
Vol 73 (3) ◽  
pp. 1029-1036 ◽  
Author(s):  
Robert A. B. van Waterschoot ◽  
Antonius E. van Herwaarden ◽  
Jurjen S. Lagas ◽  
Rolf W. Sparidans ◽  
Els Wagenaar ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Knockout Mice ◽  
Cytochrome P450 3A ◽  
Midazolam Metabolism

scholarly journals Inhibitory Effect of Polypodium Leucotomos Extract on Cytochrome P450 3A-mediated Midazolam Metabolism

2019 ◽  
Vol 31 (1) ◽  
pp. 29-39
Author(s):  
Yurika GOMI ◽  
Yuki NISHIMURA ◽  
Norimitsu KURATA ◽  
Mariko IWASE ◽  
Koichiro SHINYA ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Inhibitory Effect ◽  
Cytochrome P450 3A ◽  
Polypodium Leucotomos ◽  
Midazolam Metabolism

scholarly journals Proteomic profiling of murine biliary-derived hepatic organoids and their capacity for drug disposition, bioactivation and detoxification

2021 ◽  
Author(s):  
Lawrence Howell ◽  
Rosalind E. Jenkins ◽  
Stephen Lynch ◽  
Carrie Duckworth ◽  
B. Kevin Park ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Rna Polymerase Ii ◽  
Liver Tissue ◽  
Drug Disposition ◽  
Multiple Drug ◽  
Proteomic Profiling ◽  
Cytochrome P450 3A ◽  
Drug Induced

AbstractHepatic organoids are a recent innovation in in vitro modeling. Initial studies suggest that organoids better recapitulate the liver phenotype in vitro compared to pre-existing proliferative cell models. However, their potential for drug metabolism and detoxification remains poorly characterized, and their global proteome has yet to be compared to their tissue of origin. This analysis is urgently needed to determine what gain-of-function this new model may represent for modeling the physiological and toxicological response of the liver to xenobiotics. Global proteomic profiling of undifferentiated and differentiated hepatic murine organoids and donor-matched livers was, therefore, performed to assess both their similarity to liver tissue, and the expression of drug-metabolizing enzymes and transporters. This analysis quantified 4405 proteins across all sample types. Data are available via ProteomeXchange (PXD017986). Differentiation of organoids significantly increased the expression of multiple cytochrome P450, phase II enzymes, liver biomarkers and hepatic transporters. While the final phenotype of differentiated organoids is distinct from liver tissue, the organoids contain multiple drug metabolizing and transporter proteins necessary for liver function and drug metabolism, such as cytochrome P450 3A, glutathione-S-transferase alpha and multidrug resistance protein 1A. Indeed, the differentiated organoids were shown to exhibit increased sensitivity to midazolam (10–1000 µM) and irinotecan (1–100 µM), when compared to the undifferentiated organoids. The predicted reduced activity of HNF4A and a resulting dysregulation of RNA polymerase II may explain the partial differentiation of the organoids. Although further experimentation, optimization and characterization is needed relative to pre-existing models to fully contextualize their use as an in vitro model of drug-induced liver injury, hepatic organoids represent an attractive novel model of the response of the liver to xenobiotics. The current study also highlights the utility of global proteomic analyses for rapid and accurate evaluation of organoid-based test systems.

Cytochrome P450 3A activity in mothers and their neonates as determined by plasma 4β-hydroxycholesterol

2011 ◽  
Vol 67 (7) ◽  
pp. 715-722 ◽  
Author(s):  
Hanna Nylén ◽  
Sofia Sergel ◽  
Lisa Forsberg ◽  
Synnöve Lindemalm ◽  
Leif Bertilsson ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 3A

Metabolism of Drugs by Cytochrome P450 3A Isoforms

1995 ◽  
Vol 29 (Supplement 1) ◽  
pp. 33-44 ◽  
Author(s):  
Lisa L. von Moltke ◽  
David J. Greenblatt ◽  
Jürgen Schmider ◽  
Jerold S. Harmatz ◽  
Richard I. Shader
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 3A
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