A. Saabi, A. Allorge, D. Sauvage, F. Tournel, G. Gaulier et al., Involvement of UDP-Glucuronosyltransferases UGT1A9 and UGT2B7 in Ethanol Glucuronidation, and Interactions with Common Drugs of Abuse, Drug Metab Dispos, vol.41, issue.3, pp.568-74, 2013.
URL : https://hal.archives-ouvertes.fr/inserm-00766822

H. Al-attrache, A. Sharanek, A. Burban, M. Burbank, T. Gicquel et al., Differential sensitivity of metabolically competent and non-competent HepaRG cells to apoptosis induced by diclofenac combined or not with TNF, Toxicol Lett, vol.258, pp.71-86, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01372855

H. Andresen-streichert, A. Müller, A. Glahn, G. Skopp, and M. Sterneck, Alcohol biomarkers in clinical and forensic contexts. Dtsch Aerzteblatt Online, Internet], 2018.

C. Aninat, A. Piton, D. Glaise, L. Charpentier, T. Langouët et al., Expression of cytochromes P450, conjugating enzymes and nuclear receptors in human hepatoma HepaRG cells, Drug Metab Dispos Biol Fate Chem, vol.34, issue.1, pp.75-83, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00702085

P. Bachour-el-azzi, A. Sharanek, Z. Abdel-razzak, S. Antherieu, H. Al-attrache et al., Impact of Inflammation on Chlorpromazine-Induced Cytotoxicity and Cholestatic Features in HepaRG Cells, Drug Metab Dispos, vol.42, issue.9, pp.1556-66, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01134764

K. Balusikova and J. Kovar, Alcohol dehydrogenase and cytochrome P450 2E1 can be induced by longterm exposure to ethanol in cultured liver HEP-G2 cells, Vitro Cell Dev Biol -Anim, vol.49, issue.8, pp.619-644, 2013.

O. Blein, X. Ronot, and A. M. , Cross contamination associated with the use of multiwell culture plates for cytotoxicity assessment of volatile chemicals, Cytotechnology, vol.6, issue.1, pp.79-82, 1991.

P. Borgs, D. L. Way, M. H. Witte, and C. L. Witte, Effective stabilization of ethanol levels in multiple-well tissue culture plates, Alcohol, vol.10, issue.1, pp.31-36, 1993.

E. Borràs, C. Coutelle, A. Rosell, F. Fernández-muixi, M. Broch et al., Genetic polymorphism of alcohol dehydrogenase in europeans: TheADH2*2 allele decreases the risk for alcoholism and is associated withADH3*1, Hepatology, vol.31, issue.4, pp.984-993, 2000.

M. Bühler and K. Mann, Alcohol and the Human Brain: A Systematic Review of Different Neuroimaging Methods: alcohol and the human brain, Alcohol Clin Exp Res, vol.35, issue.10, pp.1771-93, 2011.

P. Cabarcos, I. Álvarez, M. J. Tabernero, and A. M. Bermejo, Determination of direct alcohol markers: a review, Anal Bioanal Chem, vol.407, issue.17, pp.4907-4932, 2015.

A. I. Cederbaum, Alcohol Metabolism. Clin Liver Dis, vol.16, issue.4, pp.667-85, 2012.

V. Cerec, D. Glaise, D. Garnier, S. Morosan, B. Turlin et al., Transdifferentiation of hepatocyte-like cells from the human hepatoma HepaRG cell line through bipotent progenitor, Hepatology, vol.45, issue.4, pp.957-67, 2007.
URL : https://hal.archives-ouvertes.fr/hal-00690471

R. Chou, K. Peterson, and M. Helfand, Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review, J Pain Symptom Manage, vol.28, issue.2, pp.140-75, 2004.

A. Corlu and P. Loyer, Culture Conditions Promoting Hepatocyte Proliferation and Cell Cycle Synchronization, Protocols in In Vitro Hepatocyte Research, pp.27-51, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01187298

M. H. Court, X. Zhang, X. Ding, K. K. Yee, L. M. Hesse et al., Quantitative distribution of mRNAs encoding the 19 human UDP-glucuronosyltransferase enzymes in 26 adult and 3 fetal tissues, Xenobiotica, vol.42, issue.3, pp.266-77, 2012.

H. Dahl, N. Stephanson, O. Beck, and A. Helander, Comparison of Urinary Excretion Characteristics of Ethanol and Ethyl Glucuronide, J Anal Toxicol, vol.26, issue.4, pp.201-205, 2002.

T. Do, F. Gaboriau, I. Cannie, F. Batusanski, M. Ropert et al., Iron-mediated effect of alcohol on hepatocyte differentiation in HepaRG cells, Chem Biol Interact, vol.206, issue.2, pp.117-142, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00876608

M. T. Donato, L. Tolosa, and M. J. Gómez-lechón, Culture and Functional Characterization of Human Hepatoma HepG2 Cells, Protocols in In Vitro Hepatocyte Research, pp.77-93, 2015.

H. J. Edenberg, The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants, Alcohol Res Health J Natl Inst Alcohol Abuse Alcohol, vol.30, issue.1, pp.5-13, 2007.

F. Farinati, C. S. Lieber, and A. J. Garro, Effects of chronic ethanol consumption on carcinogen activating and detoxifying systems in rat upper alimentary tract tissue, Alcohol Clin Exp Res, vol.13, issue.3, pp.357-60, 1989.

R. S. Foti and M. B. Fisher, Assessment of UDP-glucuronosyltransferase catalyzed formation of ethyl glucuronide in human liver microsomes and recombinant UGTs, Forensic Sci Int, vol.153, issue.2-3, pp.109-125, 2005.

B. Fromenty and D. Pessayre, Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity, Pharmacol Ther, vol.67, issue.1, pp.101-54, 1995.

F. J. Gonzalez, T. Ueno, M. Umeno, B. J. Song, R. L. Veech et al., Microsomal ethanol oxidizing system: transcriptional and posttranscriptional regulation of cytochrome P450, CYP2E1, Alcohol Alcohol Oxf Oxfs Suppl, vol.1, pp.97-101, 1991.

S. Guérin, A. Laplanche, A. Dunant, and C. Hill, Alcohol-attributable mortality in France, Eur J Public Health, vol.23, issue.4, pp.588-93, 2013.

C. Guguen-guillouzo, J. P. Campion, P. Brissot, D. Glaise, B. Launois et al., High yield preparation of isolated human adult hepatocytes by enzymatic perfusion of the liver, Cell Biol Int Rep, vol.6, issue.6, pp.625-633, 1982.

C. C. Halter, S. Dresen, V. Auwaerter, F. M. Wurst, and W. Weinmann, Kinetics in serum and urinary excretion of ethyl sulfate and ethyl glucuronide after medium dose ethanol intake, Int J Legal Med, vol.122, issue.2, pp.123-131, 2008.

A. Helander and O. Beck, Ethyl Sulfate: A Metabolite of Ethanol in Humans and a Potential Biomarker of Acute Alcohol Intake, J Anal Toxicol, vol.29, issue.5, pp.270-274, 2005.

L. M. Huppertz, L. Gunsilius, C. Lardi, W. Weinmann, and A. Thierauf-emberger, Influence of Gilbert's syndrome on the formation of ethyl glucuronide, Int J Legal Med, vol.129, issue.5, pp.1005-1015, 2015.

G. B. Ingall, Alcohol Biomarkers. Clin Lab Med, vol.32, issue.3, pp.391-406, 2012.

M. Ingelman-sundberg, I. Johansson, H. Yin, Y. Terelius, E. Eliasson et al., Ethanol-inducible cytochrome P4502E1: genetic polymorphism, regulation, and possible role in the etiology of alcohol-induced liver disease, Alcohol, vol.10, issue.6, pp.447-52, 1993.

A. W. Jones, Evidence-based survey of the elimination rates of ethanol from blood with applications in forensic casework, Forensic Sci Int, issue.1-3, pp.1-20, 0200.

B. S. Kaphalia, P. Cai, M. F. Khan, and A. O. Okorodudu, Ansari G a. S. Fatty acid ethyl esters: markers of alcohol abuse and alcoholism, Alcohol, vol.34, issue.2-3, pp.151-159, 2004.

T. Kardon, M. J. Coffey, G. Bánhegyi, A. A. Conley, B. Burchell et al., Transcriptional induction of bilirubin UDP-glucuronosyltransrase by ethanol in rat liver, Alcohol, vol.21, issue.3, pp.251-258, 2000.

L. Knockaert, V. Descatoire, N. Vadrot, B. Fromenty, and M. Robin, Mitochondrial CYP2E1 is sufficient to mediate oxidative stress and cytotoxicity induced by ethanol and acetaminophen, Toxicol In Vitro, vol.25, issue.2, pp.475-84, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00739823

D. R. Koop, Oxidative and reductive metabolism by cytochrome P450 2E1, FASEB J, vol.6, issue.2, pp.724-754, 1992.

N. Kummer, S. Wille, D. Fazio, V. Lambert, W. Samyn et al., A fully validated method for the quantification of ethyl glucuronide and ethyl sulphate in urine by UPLC-ESI-MS/MS applied in a prospective alcohol self-monitoring study, J Chromatogr B, vol.929, pp.149-54, 2013.

K. Kurogi, G. M. Davidson, Y. I. Mohammed, F. E. Williams, M. Liu et al., Ethanol sulfation by the human cytosolic sulfotransferases: a systematic analysis, Biol Pharm Bull, vol.35, issue.12, pp.2180-2185, 2012.

L. Daré, B. Lagente, V. Gicquel, and T. , Ethanol and its metabolites: update on toxicity, benefits, and focus on immunomodulatory effects, Drug Metab Rev, vol.51, issue.4, pp.545-61, 2019.

Y. Q. Li, D. A. Prentice, M. L. Howard, M. L. Mashford, J. S. Wilson et al., Alcohol up-regulates udpglucuronosyltransferase mrna expression in rat liver and in primary rat hepatocyte culture, Life Sci, vol.66, issue.7, pp.575-84, 2000.

C. S. Lieber, Pathogenesis and treatment of alcoholic liver disease: progress over the last 50 years, Rocz Akad Med W Bialymstoku, vol.50, pp.7-20, 1995.

A. Mahli, E. Thasler, W. Hellerbrand, and C. , Establishment of a p -nitrophenol oxidation-based assay for the analysis of CYP2E1 activity in intact hepatocytes in vitro, Toxicol Mech Methods, vol.29, issue.3, pp.219-242, 2019.

A. Michaut, L. Guillou, D. Moreau, C. Bucher, S. Mcgill et al., A cellular model to study drug-induced liver injury in nonalcoholic fatty liver disease: Application to acetaminophen, Toxicol Appl Pharmacol, vol.292, pp.40-55, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01255826

D. Nutt, L. A. King, W. Saulsbury, and C. Blakemore, Development of a rational scale to assess the harm of drugs of potential misuse. The Lancet, vol.369, pp.1047-53, 2007.

A. Obad, A. Peeran, J. I. Little, G. E. Haddad, and S. T. Tarzami, Alcohol-Mediated Organ Damages: Heart and Brain, Front Pharmacol [Internet], vol.9, 2018.

S. Ohno and S. Nakajin, Determination of mRNA Expression of Human UDP-Glucuronosyltransferases and Application for Localization in Various Human Tissues by Real-Time Reverse Transcriptase-Polymerase Chain Reaction, Drug Metab Dispos, vol.37, issue.1, pp.32-40, 2009.

N. A. Osna, T. M. Donohue, and K. K. Kharbanda, Alcoholic Liver Disease: Pathogenesis and Current Management, Alcohol Res Curr Rev, vol.38, issue.2, pp.147-61, 2017.

A. F. Pizon, C. E. Becker, and D. Bikin, The clinical significance of variations in ethanol toxicokinetics, J Med Toxicol, vol.3, issue.2, pp.63-72, 2007.

N. Quesnot, S. Bucher, C. Gade, M. Vlach, E. Vene et al., Production of chlorzoxazone glucuronides via cytochrome P4502E1 dependent and independent pathways in human hepatocytes, Arch Toxicol, vol.92, issue.10, pp.3077-91, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01863847

Z. Riches, E. L. Stanley, J. C. Bloomer, and M. Coughtrie, Quantitative Evaluation of the Expression and Activity of Five Major Sulfotransferases (SULTs) in Human Tissues: The SULT "Pie, Drug Metab Dispos, vol.37, issue.11, pp.2255-61, 2009.

A. Rogue, C. Lambert, C. Spire, C. N. Guillouzo, and A. , Interindividual Variability in Gene Expression Profiles in Human Hepatocytes and Comparison with HepaRG Cells, Drug Metab Dispos, vol.40, issue.1, pp.151-159, 2012.
URL : https://hal.archives-ouvertes.fr/hal-00865978

N. Schwab and G. Skopp, Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide, Anal Bioanal Chem, vol.406, issue.9, pp.2325-2357, 2014.

H. K. Seitz and F. Stickel, Molecular mechanisms of alcohol-mediated carcinogenesis, Nat Rev Cancer, vol.7, issue.8, pp.599-612, 2007.

A. Sharanek, A. Burban, M. Burbank, L. Guevel, R. Li et al., Rho-kinase/myosin light chain kinase pathway plays a key role in the impairment of bile canaliculi dynamics induced by cholestatic drugs, vol.6, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01326368

C. Smith, M. Gasparetto, C. Jordan, D. A. Pollyea, and V. Vasiliou, The Effects of Alcohol and Aldehyde Dehydrogenases on Disorders of Hematopoiesis, pp.349-59, 2015.

N. Stachel and G. Skopp, In vitro characterization of glucuronosyl-and sulfotransferases involved in the conjugation of ethanol, Arch Kriminol, vol.235, issue.1-2, pp.29-42, 2015.

N. Stachel and G. Skopp, Formation and inhibition of ethyl glucuronide and ethyl sulfate, Forensic Sci Int, vol.265, pp.61-65, 2016.

T. Takahashi, J. M. Lasker, A. S. Rosman, and C. S. Lieber, Induction of cytochrome P-4502E1 in the human liver by ethanol is caused by a corresponding increase in encoding messenger RNA, Hepatology, vol.17, issue.2, pp.236-281, 1993.

N. E. Walsham, R. E. Sherwood, E. Glucuronide, and . Sulfate, Advances in Clinical Chemistry, pp.47-71, 2014.

M. Winkler, G. Skopp, A. Alt, E. Miltner, J. Th et al., Comparison of direct and indirect alcohol markers with PEth in blood and urine in alcohol dependent inpatients during detoxication, Int J Legal Med, vol.127, issue.4, pp.761-769, 2013.

S. Zakhari, Overview: How Is Alcohol Metabolized by the Body?, vol.29, p.10, 2006.

A. Zhukov and M. Ingelman-sundberg, Relationship between cytochrome P450 catalytic cycling and stability: fast degradation of ethanol-inducible cytochrome P450 2E1 (CYP2E1) in hepatoma cells is abolished by inactivation of its electron donor NADPH-cytochrome P450 reductase, Biochem J, vol.340, issue.2, pp.453-461, 1999.

, Results are normalized to GAPDH gene expression. The data are expressed as the mean ± SEM for three independent experiments performed in triplicate. Statistics: **p<0.01 and *p<0.05 for cultures exposed to ethanol treatment compared with the control cultures, Liquid chromatography Mass spectrometry ? Column: C18 Accucore (10 cm) ? Temperature: 20°C temperature: 15°C ? Injected volume: 5 µL ? Source: HESI-II ? Probe: 300°C ? Mode: negative ? Spray voltage: 3 kV ? Sheath gas and auxiliary gas: N2 ? Capillary temperature: 300 °C ? Source lens: 60 V ? Acquisition data: t-SIM ? Resolution: 70,000 FWHM ? C-trap capacity: 10 6 charges ? Maximum injection time: 200 ms