Cytochrome P450 3A4 mRNA Is a More Reliable Marker than CYP3A4 Activity for Detecting Pregnane X Receptor-Activated Induction of Drug-Metabolizing Enzymes

2010 ◽  
Vol 38 (9) ◽  
pp. 1605-1611 ◽  
Author(s):  
Odette A. Fahmi ◽  
Mary Kish ◽  
Sherri Boldt ◽  
R. Scott Obach
Keyword(s):  
Cytochrome P450 ◽  
Pregnane X Receptor ◽  
Cytochrome P450 3A4 ◽  
Drug Metabolizing Enzymes ◽  
Cyp3a4 Activity ◽  
Metabolizing Enzymes ◽  
Reliable Marker

scholarly journals Sesquiterpenes Are Agonists of the Pregnane X Receptor but Do Not Induce the Expression of Phase I Drug-Metabolizing Enzymes in the Human Liver

2019 ◽  
Vol 20 (18) ◽  
pp. 4562
Author(s):  
Michaela Šadibolová ◽  
Tomáš Zárybnický ◽  
Tomáš Smutný ◽  
Petr Pávek ◽  
Zdeněk Šubrt ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Phase I ◽  
Reporter Gene ◽  
Pregnane X Receptor ◽  
Receptor Interaction ◽  
Cytochrome P450 3A4 ◽  
Drug Metabolizing Enzymes ◽  
Metabolizing Enzymes ◽  
Protein Levels ◽  
Reporter Gene Assays

Sesquiterpenes, the main components of plant essential oils, are bioactive compounds with numerous health-beneficial activities. Sesquiterpenes can interact with concomitantly administered drugs due to the modulation of drug-metabolizing enzymes (DMEs). The aim of this study was to evaluate the modulatory effects of six sesquiterpenes (farnesol, cis-nerolidol, trans-nerolidol, α-humulene, β-caryophyllene, and caryophyllene oxide) on the expression of four phase I DMEs (cytochrome P450 3A4 and 2C, carbonyl reductase 1, and aldo-keto reductase 1C) at both the mRNA and protein levels. For this purpose, human precision-cut liver slices (PCLS) prepared from 10 patients and transfected HepG2 cells were used. Western blotting, quantitative real-time PCR and reporter gene assays were employed in the analyses. In the reporter gene assays, all sesquiterpenes significantly induced cytochrome P450 3A4 expression via pregnane X receptor interaction. However in PCLS, their effects on the expression of all the tested DMEs at the mRNA and protein levels were mild or none. High inter-individual variabilities in the basal levels as well as in modulatory efficacy of the tested sesquiterpenes were observed, indicating a high probability of marked differences in the effects of these compounds among the general population. Nevertheless, it seems unlikely that the studied sesquiterpenes would remarkably influence the bioavailability and efficacy of concomitantly administered drugs.

scholarly journals A Double Transgenic Mouse Model Expressing Human Pregnane X Receptor and Cytochrome P450 3A4

2008 ◽  
Vol 36 (12) ◽  
pp. 2506-2512 ◽  
Author(s):  
Xiaochao Ma ◽  
Connie Cheung ◽  
Kristopher W. Krausz ◽  
Yatrik M. Shah ◽  
Ting Wang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Pregnane X Receptor ◽  
Transgenic Mouse Model ◽  
Cytochrome P450 3A4 ◽  
Double Transgenic Mouse

scholarly journals Gambogic acid suppresses cytochrome P450 3A4 by downregulating pregnane X receptor and up-regulating DEC1 in human hepatoma HepG2 cells

2015 ◽  
Vol 4 (4) ◽  
pp. 1059-1071 ◽  
Author(s):  
Wei Liu ◽  
Rui Ning ◽  
Rui-Ni Chen ◽  
Jin-Hua Hu ◽  
Hai-Yan Gui ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Hepg2 Cells ◽  
Pregnane X Receptor ◽  
Gambogic Acid ◽  
Cytochrome P450 3A4 ◽  
Human Hepatoma ◽  
Human Hepatoma Hepg2 Cells ◽  
Hepatoma Hepg2

Gambogic acid suppresses cytochrome P450 3A4 by downregulating pregnane X receptor and up-regulating DEC1 in human hepatoma HepG2 cells.

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