scholarly journals Acetyl Tributyl Citrate, the Most Widely Used Phthalate Substitute Plasticizer, Induces Cytochrome P450 3A through Steroid and Xenobiotic Receptor

2011 ◽  
Vol 123 (2) ◽  
pp. 460-470 ◽  
Author(s):  
Akira Takeshita ◽  
Junko Igarashi-Migitaka ◽  
Kazusa Nishiyama ◽  
Hideyo Takahashi ◽  
Yasuhiro Takeuchi ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 3A ◽  
Steroid And Xenobiotic Receptor ◽  
Acetyl Tributyl Citrate ◽  
Xenobiotic Receptor

Induction of Cytochrome P450 3A by Paclitaxel in Mice: Pivotal Role of the Nuclear Xenobiotic Receptor, Pregnane X Receptor

2003 ◽  
Vol 31 (5) ◽  
pp. 681-684 ◽  
Author(s):  
Srikanth C. Nallani ◽  
Bryan Goodwin ◽  
Jodi M. Maglich ◽  
Donna J. Buckley ◽  
Arthur R. Buckley ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Pregnane X Receptor ◽  
Pivotal Role ◽  
Cytochrome P450 3A ◽  
Xenobiotic Receptor

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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