Critical role of cytochrome P450 2E1 (CYP2E1) in the development of high fat-induced non-alcoholic steatohepatitis, J Hepatol, vol.57, pp.860-866, 2012. ,
Cytokines down-regulate expression of major cytochrome P-450 enzymes in adult human hepatocytes in primary culture, Mol Pharmacol, vol.44, pp.707-715, 1993. ,
Expression of cytochrome P450, conjugating enzymes and nuclear receptors in human hepatoma HepaRG cells, Drug Metab Dispos, vol.34, pp.75-83, 2006. ,
Increased expression of cytochrome P450 2E1 in nonalcoholic fatty liver disease: Mechanisms and pathophysiological role, Clin Res Hepatol Gastroenterol, vol.35, pp.630-637, 2011. ,
URL : https://hal.archives-ouvertes.fr/hal-00739365
Conjugation of 1-naphtol in primary cell cultures of rat ovarian cells, Chem Biol Interact, vol.124, pp.103-118, 2000. ,
Both cytochromes P450 2E1 and 1A1 are involved in the metabolism of chlorzoxazone, Chem Res Toxicol, vol.6, pp.852-857, 1993. ,
Methodology to assay CYP2E1 mixed function oxidase catalytic activity and its induction, Redox Biol, vol.2, pp.1048-1054, 2014. ,
Transdifferentiation of hepatocyte-like cells from the human hepatoma HepaRG cell line through bipotent progenitor, Hepatology, vol.45, pp.957-967, 2007. ,
URL : https://hal.archives-ouvertes.fr/hal-00690471
Hepatic cytochrome P450 2E1 activity in nondiabetic patients with nonalcoholic steatohepatitis, Hepatology, vol.37, pp.544-550, 2003. ,
Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review, J Pain Symptom Manage, vol.28, pp.140-75, 2004. ,
Physiological disposition and metabolic fate of chlorzoxazone (paraflex) in man, J Pharmacol Exp Ther, vol.128, pp.340-343, 1960. ,
The metabolic fate of zoxazolamine (flexin) in man, 1960. ,
, J Pharmacol Exp Ther, vol.128, pp.333-339
Pharmacokinetics of chlorzoxazone in humans, J Pharm Sci, vol.72, pp.991-994, 1983. ,
Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines, Tox Appl Pharmacol, vol.249, pp.91-100, 2010. ,
URL : https://hal.archives-ouvertes.fr/hal-00742145
Robustness of chlorzoxazone as an in vivo measure of cytochrome P450 2E1 activity, Br J Clin Pharmacol, vol.58, pp.190-200, 2004. ,
Use of chlorzoxazone as an in vivo probe of cytochrome P450 2E1: choice of dose and phenotypic trait measure, J Clin Pharmacol, vol.38, pp.82-89, 1998. ,
, The CYTONOX trial Dan Med J, vol.63, 2016.
Higher chlorzoxazone clearance in obese children compared with nonobese peers, Br J Clin Pharmacol, vol.84, pp.1738-1747, 2018. ,
, , 2006.
, Brodie Award Lecture. CYP2E1. Drug Metab Dispos, vol.35, pp.1-8
Evaluation of HepaRG cells as an in vitro model for human drug metabolism studies, Drug Metab. Dispos, vol.36, pp.1444-1452, 2008. ,
Single-dose disulfiram inhibition of chlorzoxazone metabolism: a clinical probe for P450 2E1, Clin Pharmacol Ther, vol.53, pp.643-650, 1993. ,
Oxidative and reductive metabolism by cytochrome P450 2E1, FASEB J, vol.6, pp.724-730, 1982. ,
Chlorzoxazone, a selective probe for phenotyping CYP2E1 in humans, Pharmacogenetics, vol.9, pp.377-88, 1999. ,
Increased susceptibility of natural killer T-cell-deficient mice to acetaminophen-induced liver injury, Hepatology, vol.57, pp.1575-1584, 2013. ,
Identification of a 16-nucleotide sequence that mediates post-transcriptional regulation of rat CYP2E1 by insulin, J Bio. Chem, vol.277, pp.45904-45910, 2002. ,
Clinical experience with chlorzoxazone (paraflex) in neurologic disorders, Med Bull (Ann Arbor), vol.24, pp.259-264, 1958. ,
Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P-450IIE1, Chem Res Toxicol, vol.3, pp.566-573, 1990. ,
The effect of endotoxin administration on the pharmacokinetics of chlorzoxazone in humans, Clin Pharmacol Ther, vol.66, pp.554-562, 1999. ,
Three-dimensional HepaRG model as an attractive tool for toxicity testing, Toxicol Sci, vol.130, pp.106-122, 2012. ,
High-performance liquid chromatographic determination of chlorzoxazone and 6-hydroxychlorzoxazone in serum: a tool for indirect evaluation of cytochrome P4502E1 activity in humans, J Chromatogr, vol.622, pp.79-86, 1993. ,
Hepatic disposition of the cytochrome P450 2E1 marker chlorzoxazone and its hydroxylated metabolite in isolated perfused rat livers, J Pharm Sci, vol.95, pp.1414-1424, 2006. ,
In vitro-in vivo correlation for drugs and other compounds eliminated by glucuronidation in humans: pitfalls and promises, Biochem Pharmacol, vol.71, pp.1531-1539, 2006. ,
Evaluation of genotoxicity using automated detection of ?H2AX in metabolically competent HepaRG cells, Mutagenesis, vol.31, pp.43-50, 2016. ,
Effect of the acute-phase response on the pharmacokinetics of chlorzoxazone and cytochrome P-450 2E1 in vitro activity in rats, Drug Metab Dispos, vol.27, p.1074, 1999. ,
The UDP-glucurosyltransferases: Their role in drug metabolism and detoxification, Int J Biochem Cell Biol, vol.45, pp.1121-1153, 2013. ,
A cocktail approach for assessing the in vitro activity of human cytochrome P450s : An overview of current methodologies, J Pharm Biomed Anal, vol.101, pp.221-237, 2014. ,
Induction of rat hepatic Nnitrosodimethylamine demethylase by acetone is due to protein stabilization, J Biol Chem, vol.264, pp.3568-3572, 1989. ,
Identification of chlorzoxazone metabolites in human urine, Arzneimittelforschung, vol.32, pp.759-763, 1982. ,
Honigberg IL (1970) Determination of degradation kinetics of chlorzoxazone by thin-layer chromatography, J Chromatogr, vol.46, pp.211-216 ,
Optimized assays for human UDP-glucuronosyltransferase (UGT) activities: altered alamethicin concentration and utility to screen for UGT inhibitors, Drug Metab Dispos, vol.40, pp.1051-1065, 2012. ,
Ultrasensitive tandem mass spectrometry after chlorzoxazone microdosing, J Chromato, vol.1027, pp.207-213, 2016. ,
Insulin signaling in the transcriptional and posttranscriptional regulation of CYP2E1 expression, Hepatology, vol.35, pp.263-273, 2002. ,
Effects of fatty acids and ketone bodies on cytochromes P450, 1997. ,
, 2B, 4A, and 2E1 expression in primary cultured rat hepatocytes, Arch Biochem Biophys, vol.138, pp.217-224
, O cells) and subjected (+ ?-glucuronidase) or not (-?-glucuronidase) to ?-glucuronidase hydrolysis. B) Culture medium with CHZ incubated with parental HepG2 cells or recombinant HepG2-CYP2E1 cells without
, ?-glucuronidase hydrolysis prior HPLC-UV analysis. C) Culture medium with CHZ incubated with differentiated parental HepaRG or recombinant HepaRG-CYP2E1 cells without (-?glucuronidase) or with (+?-glucuronidase) ?-glucuronidase hydrolysis prior HPLC-UV analysis. D) Culture medium with CHZ
, parental and CYP2E1 expressing HepG2 and HepaRG cells following HPLC-UV analysis of culture media, without (-?-glucuronidase, left graph) or with (+?glucuronidase, right graph) ?-glucuronidase hydrolysis of media. Statistics: 2 or 3 independent experiments with 6 or 9 independent culture wells, ? p<0.01: OH-CHZ significantly higher in HepaRG and HepaRG-CYP2E1 versus HepG2, ? ? p <0.01: OH-CHZ significantly higher in HH versus HepaRG, HepaRGCYP2E1 and HepG2, ? ? ? p<0.01: OH-CHZ significantly higher in HepG2 CYP2E1 than all others cells. Graph with ?-glucuronidase hydrolysis (+?-glucuronidase), § § p <0.001: OH-CHZ significantly higher in parental HepaRG versus HepG2, § § § p<0.001 OH-CHZ significantly higher in HepG2-CYP2E1, HepaRG CYP2E1 and HH versus HepaRG and HepG2 WT. F)
, Quantification of CHZ-O-and CHZ-N-Glc activities (pmoles/min/mg of total proteins
HepaRG CYP2E1 cells and primary hepatocytes (HH), CHZ-O-Glc significantly higher in HepaRG versus HepG2 CYP2E1 cells and significantly higher in HepaRG-CYP2E1 and primary hepatocytes, vol.01 ,
, Statistics of CHZ-N-Glc graph, § § § p<0.001 CHZ-N-Glc significantly higher in primary hepatocytes (HH) versus HepG2 CYP2E1, and § § p<0.01 parental HepaRG and HepaRG-CYP2E1 cells versus primary hepatocytes (HH) and HepG2 CYP2E1. Figure 3: Conversion of OH-CHZ into CHZ-O-Glc in HepaRG cells and human hepatocytes, versus HepaRG and HepG2 CYP2E1
, A) HPLC-UV chromatograms of the time-course analysis of OH-CHZ conversion into CHZ
by HepaRG cells at 0, 15, 60 and 90 min. B) Quantification in ?M of OH-CHZ (plain lane) and CHZ-O-Glc ,
/min/mg of total proteins) after 90 min of 25 incubation of culture medium containing OH-CHZ by HepG2 CYP2E1, HepaRG, HepaRG CYP2E1 cells and primary hepatocytes (HH). Statistics, § § § p<0, CHZ-O-Glc significantly higher in HepaRG, HepaRG-CYP2E1 cells and primary hepatocytes (HH) versus HepG2, vol.001 ,
, Figure 4: Inhibition of CHZ-O-Glc and CHZ-N-Glc production by pentachlorophenol
Glc in culture media of HepaRG cells after a 90 min incubation with CHZ in absence (0 ?M) or presence of pentacholorophenol (PCP) at 10 and 100 ?M. The 2 main contaminating peaks are indicated (*). B) Quantification of OH-CHZ activities (pmoles/min/mg of total proteins) in culture of primary hepatocytes (HH), parental and CYP2E1 expressing HepaRG cells and HepG2 CYP2E1 cells in absence ,
, parental and CYP2E1 expressing HepaRG cells in absence and presence of various concentrations of PCP (2.5 to 100 ?M). D) Quantification of CHZ-O-Glc activities (pmoles/min/mg of total proteins) in culture of primary hepatocytes (HH) and parental HepaRG cells in absence and presence of various concentrations of PCP (2.5 to 100 ?M), Glc activities (pmoles/min/mg of total proteins) in culture of primary hepatocytes (HH)
, Production of CHZ-O and CHZ-N-Glc in recombinant HepG2-UGT cells, vol.5
CHZ-N-Glc (grey bars) and OH-CHZ (dark bars) in culture medium of recombinant HepG2 cells expressing either UGT1A1, 1A6 or 1A9, and HepG2 cells expression CYP2E1 and UGT1A1, ?M) of CHZ-O-Glc (white bars), pp.1-6 ,
, CHZ (B) and the production of both CHZ-O-Glc and CHZ-N-Glc was analyzed by HPLC and quantified. Statistics, A) Chart for cells incubated with OH-CHZ: § p<0.05 OH-CHZ significantly lower and * p<0.01 CHZ-OGlc significantly higher in cells expressing UGT1A1, 1A6 and 1A9 versus parental/wild type (WT) HepG2 and HepG2-CYP2E1, B) chart for cells incubated with CHZ: * p<0.01 CHZ-OGlc significantly higher in HepG2 cells expressing CYP2E1 and UGT1A1, 1A6 or 1A9 versus all other conditions, vol.29, p.31