961
Views
50
CrossRef citations to date
0
Altmetric
Review Article

A comprehensive review of cytochrome P450 2E1 for xenobiotic metabolism

, , , , ORCID Icon &
Pages 178-195 | Received 02 Apr 2019, Accepted 13 Jun 2019, Published online: 28 Jun 2019

References

  • Aljomah G, Baker SS, Liu W, Kozielski R, Oluwole J, Lupu B, Baker RD, Zhu L. 2015. Induction of CYP2E1 in non-alcoholic fatty liver diseases. Exp Mol Pathol. 99:677–681.
  • Anandatheerthavarada HK, Addya S, Dwivedi RS, Biswas G, Mullick J, Avadhani NG. 1997. Localization of multiple forms of inducible cytochromes P450 in rat liver mitochondria: immunological characteristics and patterns of xenobiotic substrate metabolism. Arch Biochem Biophys. 339:136–150.
  • Ande A, Sinha N, Rao PS, McArthur CP, Ayuk L, Achu PN, Njinda A, Kumar A, Kumar S. 2015. Enhanced oxidative stress by alcohol use in HIV + patients: possible involvement of cytochrome P450 2E1 and antioxidant enzymes. AIDS Res Ther. 12:29.
  • Arici M, Ozhan G. 2017. The genetic profiles of CYP1A1, CYP1A2 and CYP2E1 enzymes as susceptibility factor in xenobiotic toxicity in Turkish population. Saudi Pharm J. 25:294–297.
  • Bansal S, Anandatheerthavarada HK, Prabu GK, Milne GL, Martin MV, Guengerich FP, Avadhani NG. 2013. Human cytochrome P450 2E1 mutations that alter mitochondrial targeting efficiency and susceptibility to ethanol-induced toxicity in cellular models. J Biol Chem. 288:12627–12644.
  • Barbier-Torres L, Iruzubieta P, Fernandez-Ramos D, Delgado TC, Taibo D, Guitierrez-de JV, Varela-Rey M, Azkargorta M, Navasa N, Fernandez-Tussy P, et al. 2017. The mitochondrial negative regulator MCJ is a therapeutic target for acetaminophen-induced liver injury. Nat Commun. 8:2068.
  • Bellward GD, Chang T, Rodrigues B, McNeill JH, Maines S, Ryan DE, Levin W, Thomas PE. 1988. Hepatic cytochrome P-450j induction in the spontaneously diabetic BB rat. Mol Pharmacol. 33:140–143.
  • Bianchino G, Cittadini A, Grieco V, Traficante A, Zupa A, Improta G, Aieta M, Sgambato A. 2011. Polymorphisms of the CYP1A1, CYP2E1 and XRCC1 genes and cancer risk in a Southern Italian population: a case-control study. Anticancer Res. 31:1359–1365.
  • Boadas-Vaello P, Jover E, Saldana-Ruiz S, Soler-Martin C, Chabbert C, Bayona JM, Llorens J. 2009. Allylnitrile metabolism by CYP2E1 and other CYPs leads to distinct lethal and vestibulotoxic effects in the mouse. Toxicol Sci: Off J Soc Toxicol. 107:461–472.
  • Bogaards JJ, Bertrand M, Jackson P, Oudshoorn MJ, Weaver RJ, van Bladeren PJ, Walther B. 2000. Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man. Xenobiotica. 30:1131–1152.
  • Boussadia B, Ghosh C, Plaud C, Pascussi JM, de Bock F, Rousset MC, Janigro D, Marchi N. 2014. Effect of status epilepticus and antiepileptic drugs on CYP2E1 brain expression. Neuroscience. 281:124–134.
  • Brady JF, Ishizaki H, Fukuto JM, Lin MC, Fadel A, Gapac JM, Yang CS. 1991. Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolites. Chem Res Toxicol. 4:642–647.
  • Brocic M, Supic G, Zeljic K, Jovic N, Kozomara R, Zagorac S, Zlatkovic M, Magic Z. 2011. Genetic polymorphisms of ADH1C and CYP2E1 and risk of oral squamous cell carcinoma. Otolaryngol Head Neck Surg. 145:586–593.
  • Caldwell JC, Keshava N. 2006. Key issues in the modes of action and effects of trichloroethylene metabolites for liver and kidney tumorigenesis. Environ Health Perspect. 114:1457–1463.
  • Caro AA, Cederbaum AI. 2005. Inhibition of CYP2E1 catalytic activity in vitro by S-adenosyl-L-methionine. Biochem Pharmacol. 69:1081–1093.
  • Carriere V, Goasduff T, Ratanasavanh D, Morel F, Gautier JC, Guillouzo A, Beaune P, Berthou F. 1993. Both cytochromes P450 2E1 and 1A1 are involved in the metabolism of chlorzoxazone. Chem Res Toxicol. 6:852–857.
  • Cederbaum AI. 2012. Alcohol metabolism. Clin Liver Dis. 16:667–685.
  • Cederbaum AI. 2013. Nrf2 and antioxidant defense against CYP2E1 toxicity. Sub-cellular Biochem. 67:105–130.
  • Cederbaum AI, Lu Y, Wu D. 2009. Role of oxidative stress in alcohol-induced liver injury. Arch Toxicol. 83:519–548.
  • Chang LS, Hsu YW, Lu CC, Lo MH, Hsieh KS, Li SC, Chang WC, Kuo HC. 2017. CYP2E1 gene polymorphisms related to the formation of coronary artery lesions in Kawasaki disease. Pediatr Infect Dis J. 36:1039–1043.
  • Chaudhuri SR, Mukherjee S, Paul RR, Haldar A, Chaudhuri K. 2013. CYP1AI and CYP2E1 gene polymorphisms may increase susceptibility to oral submucous fibrosis among betel quid chewers of eastern India. Gene. 513:268–271.
  • Chen W, Koenigs LL, Thompson SJ, Peter RM, Rettie AE, Trager WF, Nelson SD. 1998. Oxidation of acetaminophen to its toxic quinone imine and nontoxic catechol metabolites by baculovirus-expressed and purified human cytochromes P450 2E1 and 2A6. Chem Res Toxicol. 11:295–301.
  • Chen T, Mittelstaedt RA, Beland FA, Heflich RH, Moore MM, Parsons BL. 2005. 4-Aminobiphenyl induces liver DNA adducts in both neonatal and adult mice but induces liver mutations only in neonatal mice. Int J Cancer. 117:182–187.
  • Chen H, Zhang X, Feng Y, Rui W, Shi Z, Wu L. 2014. Bioactive components of Glycyrrhiza uralensis mediate drug functions and properties through regulation of CYP450 enzymes. Mol Med Rep. 10:1355–1362.
  • Cheng J, Krausz KW, Li F, Ma X, Gonzalez FJ. 2013. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid. Toxicol Appl Pharmacol. 266:245–253.
  • Choi H, Tabashidze N, Rossner P Jr, Dostal M, Pastorkova A, Kong SW, Gmuender H, Sram RJ. 2017. Altered vulnerability to asthma at various levels of ambient Benzo[a]Pyrene by CTLA4, STAT4 and CYP2E1 polymorphisms. Environ Pollut. 231:1134–1144.
  • Couto N, Al-Majdoub ZM, Achour B, Wright PC, Rostami-Hodjegan A, Barber J. 2019. Quantification of proteins involved in drug metabolism and disposition in the human liver using label-free global proteomics. Mol Pharm. 16:632–647.
  • Deka M, Bose M, Baruah B, Bose PD, Medhi S, Bose S, Saikia A, Kar P. 2010. Role of CYP2E1 gene polymorphisms association with hepatitis risk in Northeast India. World J Gastroenterol. 16:4800–4808.
  • Ding WX, Li M, Chen X, Ni HM, Lin CW, Gao W, Lu B, Stolz DB, Clemens DL, Yin XM. 2010. Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice. Gastroenterology. 139:1740–1752.
  • Donato MT, Lahoz A, Jimenez N, Perez G, Serralta A, Mir J, Castell JV, Gomez LM. 2006. Potential impact of steatosis on cytochrome P450 enzymes of human hepatocytes isolated from fatty liver grafts. Drug Metab Dispos. 34:1556–1562.
  • Ekstrom G, Ingelman-Sundberg M. 1989. Rat liver microsomal NADPH-supported oxidase activity and lipid peroxidation dependent on ethanol-inducible cytochrome P-450 (P-450IIE1). Biochem Pharmacol. 38:1313–1319.
  • El Hadri L, Chanas B, Ghanayem BI. 2005. Comparative metabolism of methacrylonitrile and acrylonitrile to cyanide using cytochrome P4502E1 and microsomal epoxide hydrolase-null mice. Toxicol Appl Pharmacol. 205:116–125.
  • Emery MG, Jubert C, Thummel KE, Kharasch ED. 1999. Duration of cytochrome P-450 2E1 (CYP2E1) inhibition and estimation of functional CYP2E1 enzyme half-life after single-dose disulfiram administration in humans. J Pharmacol Exp Ther. 291:213–219.
  • Fang Z, Wu Y, Zhang N. 2017. Association between CYP2E1 genetic polymorphisms and urinary cancer risk: a meta-analysis. Oncotarget. 8:86853–86864.
  • Ferguson CS, Tyndale RF. 2011. Cytochrome P450 enzymes in the brain: emerging evidence of biological significance. Trends Pharmacol Sci. 32:708–714.
  • Fontecave M, Atta M, Mulliez E. 2004. S-adenosylmethionine: nothing goes to waste. Trends Biochem Sci. 29:243–249.
  • French SW. 2013. The importance of CYP2E1 in the pathogenesis of alcoholic liver disease and drug toxicity and the role of the proteasome. Subcell Biochem. 67:145–164.
  • Gan J, Skipper PL, Tannenbaum SR. 2001. Oxidation of 2,6-dimethylaniline by recombinant human cytochrome P450s and human liver microsomes. Chem Res Toxicol. 14:672–677.
  • Garbutt JC, West SL, Carey TS, Lohr KN, Crews FT. 1999. Pharmacological treatment of alcohol dependence: a review of the evidence. JAMA. 281:1318–1325.
  • Gebhardt AC, Lucas D, Menez JF, Seitz HK. 1997. Chlormethiazole inhibition of cytochrome P450 2E1 as assessed by chlorzoxazone hydroxylation in humans. Hepatology. 26:957–961.
  • Gill P, Bhattacharyya S, McCullough S, Letzig L, Mishra PJ, Luo C, Dweep H, James L. 2017. MicroRNA regulation of CYP 1A2, CYP3A4 and CYP2E1 expression in acetaminophen toxicity. Sci Rep. 7:12331.
  • Goh LP, Chong ET, Chua KH, Chuah JA, Lee PC. 2014. Significant genotype difference in the CYP2E1 PstI polymorphism of indigenous groups in Sabah, Malaysia with Asian and non-Asian populations. Asian Pac J Cancer Prev. 15:7377–7381.
  • Gordillo-Bastidas E, Panduro A, Gordillo-Bastidas D, Zepeda-Carrillo EA, Garcia-Banuelos JJ, Munoz-Valle JF, Bastidas-Ramirez BE. 2010. Polymorphisms of alcohol metabolizing enzymes in indigenous Mexican population: unusual high frequency of CYP2E1*c2 allele. Alcohol Clin Exp Res. 34:142–149.
  • Groer C, Busch D, Patrzyk M, Beyer K, Busemann A, Heidecke CD, Drozdzik M, Siegmund W, Oswald S. 2014. Absolute protein quantification of clinically relevant cytochrome P450 enzymes and UDP-glucuronosyltransferases by mass spectrometry-based targeted proteomics. J Pharm Biomed Anal. 100:393–401.
  • Groll N, Petrikat T, Vetter S, Colnot S, Weiss F, Poetz O, Joos TO, Rothbauer U, Schwarz M, Braeuning A. 2016. Coordinate regulation of Cyp2e1 by beta-catenin- and hepatocyte nuclear factor 1alpha-dependent signaling. Toxicology. 350–352:40–48.
  • Guaoua S, Ratbi I, Laarabi FZ, Elalaoui SC, Jaouad IC, Barkat A, Sefiani A. 2014. Distribution of allelic and genotypic frequencies of NAT2 and CYP2E1 variants in Moroccan population. BMC Genet. 15:156.
  • Guengerich FP. 1991. Reactions and significance of cytochrome P-450 enzymes. J Biol Chem. 266:10019–10022.
  • Guengerich FP. 1997. Comparisons of catalytic selectivity of cytochrome P450 subfamily enzymes from different species. Chem-Biol Interact. 106:161–182.
  • Hajovsky H, Hu G, Koen Y, Sarma D, Cui W, Moore DS, Staudinger JL, Hanzlik RP. 2012. Metabolism and toxicity of thioacetamide and thioacetamide S-oxide in rat hepatocytes. Chem Res Toxicol. 25:1955–1963.
  • Hartman JH, Boysen G, Miller GP. 2012. CYP2E1 metabolism of styrene involves allostery. Drug Metab Dispos. 40:1976–1983.
  • Hartman JH, Letzig LG, Roberts DW, James LP, Fifer EK, Miller GP. 2015a. Cooperativity in CYP2E1 metabolism of acetaminophen and styrene mixtures. Biochem Pharmacol. 97:341–349.
  • Hartman JH, Martin HC, Caro AA, Pearce AR, Miller GP. 2015b. Subcellular localization of rat CYP2E1 impacts metabolic efficiency toward common substrates. Toxicology. 338:47–58.
  • Hartman JH, Miller GP, Meyer JN. 2017. Toxicological implications of mitochondrial localization of CYP2E1. Toxicol Res. 6:273–289.
  • Hayashi S, Watanabe J, Kawajiri K. 1991. Genetic polymorphisms in the 5'-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J Biochem. 110:559–565.
  • Higuchi R, Fukami T, Nakajima M, Yokoi T. 2013. Prilocaine- and lidocaine-induced methemoglobinemia is caused by human carboxylesterase-, CYP2E1-, and CYP3A4-mediated metabolic activation. Drug Metab Dispos. 41:1220–1230.
  • Hinson JA, Roberts DW, James LP. 2010. Mechanisms of acetaminophen-induced liver necrosis. Handb Exp Pharmacol. 369–405.
  • Hu Y, Hakkola J, Oscarson M, Ingelman-Sundberg M. 1999. Structural and functional characterization of the 5'-flanking region of the rat and human cytochrome P450 2E1 genes: identification of a polymorphic repeat in the human gene. Biochem Biophys Res Commun. 263:286–293.
  • Ingelman-Sundberg M, Johansson I. 1984. Mechanisms of hydroxyl radical formation and ethanol oxidation by ethanol-inducible and other forms of rabbit liver microsomal cytochromes P-450. J Biol Chem. 259:6447–6458.
  • Ingelman-Sundberg M, Johansson I, Yin H, Terelius Y, Eliasson E, Clot P, Albano E. 1993. Ethanol-inducible cytochrome P4502E1: genetic polymorphism, regulation, and possible role in the etiology of alcohol-induced liver disease. Alcohol. 10:447–452.
  • Ingelman-Sundberg M, Ronis MJ, Lindros KO, Eliasson E, Zhukov A. 1994. Ethanol-inducible cytochrome P4502E1: regulation, enzymology and molecular biology. Alcohol Alcoholism (Oxford, Oxfordshire) Supplement. 2:131–139.
  • Inoue K, Yamazaki H, Shimada T. 2000. Characterization of liver microsomal 7-ethoxycoumarin O-deethylation and chlorzoxazone 6-hydroxylation activities in Japanese and Caucasian subjects genotyped for CYP2E1 gene. Arch Toxicol. 74:372–378.
  • Ioannides C. 1996. Cytochromes P450: metabolic and toxicological aspects. Boca Rotan (FL): CRC Press.
  • Ishizaki H, Brady JF, Ning SM, Yang CS. 1990. Effect of phenethyl isothiocyanate on microsomal N-nitrosodimethylamine metabolism and other monooxygenase activities. Xenobiotica; Fate Foreign Compounds Biol Syst. 20:255–264.
  • Jamwal R, Barlock BJ, Adusumalli S, Ogasawara K, Simons BL, Akhlaghi F. 2017. Multiplex and label-free relative quantification approach for studying protein abundance of drug metabolizing enzymes in human liver microsomes using SWATH-MS. J Proteome Res. 16:4134–4143.
  • Jiang S, Vozmediano V. 2019. Acetaminophen protein adducts in hospitalized children receiving multiple doses of acetaminophen. J Clin Pharmacol.
  • Jin M, Ande A, Kumar A, Kumar S. 2013. Regulation of cytochrome P450 2e1 expression by ethanol: role of oxidative stress-mediated pkc/jnk/sp1 pathway. Cell Death Dis. 4:e554.
  • Johansson I, Ingelman-Sundberg M. 1985. Carbon tetrachloride-induced lipid peroxidation dependent on an ethanol-inducible form of rabbit liver microsomal cytochrome P-450. FEBS Lett. 183:265–269.
  • Johnsrud EK, Koukouritaki SB, Divakaran K, Brunengraber LL, Hines RN, McCarver DG. 2003. Human hepatic CYP2E1 expression during development. J Pharmacol Exp Ther. 307:402–407.
  • Kakino K, Kiyohara C, Horiuchi T, Nakanishi Y. 2016. CYP2E1 rs2031920, COMT rs4680 polymorphisms, cigarette smoking, alcohol use and lung cancer risk in a Japanese population. Asian Pac J Cancer Prev. 17:4063–4070.
  • Karmakar S, Banik NL, Patel SJ, Ray SK. 2007. Garlic compounds induced calpain and intrinsic caspase cascade for apoptosis in human malignant neuroblastoma SH-SY5Y cells. Apoptosis: Int J Programmed Cell Death. 12:671–684.
  • Kathirvel E, Chen P, Morgan K, French SW, Morgan TR. 2010. Oxidative stress and regulation of anti-oxidant enzymes in cytochrome P4502E1 transgenic mouse model of non-alcoholic fatty liver. J Gastroenterol Hepatol. 25:1136–1143.
  • Kayaalti Z, Soylemezoglu T. 2010. Distribution of ADH1B, ALDH2, CYP2E1 *6, and CYP2E1 *7B genotypes in Turkish population. Alcohol. 44:415–423.
  • Khan RA, Khan MR, Sahreen S. 2012. CCl4-induced hepatotoxicity: protective effect of rutin on p53, CYP2E1 and the antioxidative status in rat. BMC Complement Altern Med. 12:178.
  • Khemawoot P, Yokogawa K, Shimada T, Miyamoto K. 2007. Obesity-induced increase of CYP2E1 activity and its effect on disposition kinetics of chlorzoxazone in Zucker rats. Biochem Pharmacol. 73:155–162.
  • Krasniak AE, Knipp GT, Svensson CK, Liu W. 2014. Pharmacogenomics of acetaminophen in pediatric populations: a moving target. Front Genet. 5:314.
  • Kraus D, Rokitta D, Fuhr U, Tomalik-Scharte D. 2013. The role of human cytochrome P450 enzymes in metabolism of acrylamide in vitro. Toxicol Mech Methods. 23:346–351.
  • Krishnakumar D, Gurusamy U, Dhandapani K, Surendiran A, Baghel R, Kukreti R, Gangadhar R, Prayaga U, Manjunath S, Adithan C. 2012. Genetic polymorphisms of drug-metabolizing phase I enzymes CYP2E1, CYP2A6 and CYP3A5 in South Indian population. Fundam Clin Pharmacol. 26:295–306.
  • Kumar S, Jin M, Ande A, Sinha N, Silverstein PS, Kumar A. 2012. Alcohol consumption effect on antiretroviral therapy and HIV-1 pathogenesis: role of cytochrome P450 isozymes. Expert Opin Drug Metab Toxicol. 8:1363–1375.
  • Kumar S, Sinha N, Gerth KA, Rahman MA, Yallapu MM, Midde NM. 2017. Specific packaging and circulation of cytochromes P450, especially 2E1 isozyme, in human plasma exosomes and their implications in cellular communications. Biochem Biophys Res Commun. 491:675–680.
  • Laethem RM, Balazy M, Falck JR, Laethem CL, Koop DR. 1993. Formation of 19(S)-, 19(R)-, and 18(R)-hydroxyeicosatetraenoic acids by alcohol-inducible cytochrome P450 2E1. J Biol Chem. 268:12912–12918.
  • Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, Reisch JS, Schiodt FV, Ostapowicz G, Shakil AO. 2005. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 42:1364–1372.
  • Lash LH, Fisher JW, Lipscomb JC, Parker JC. 2000. Metabolism of trichloroethylene. Environ Health Perspect. 108:177–200.
  • Lau AH. 1999. Apoptosis induced by cisplatin nephrotoxic injury. Kidney Int. 56:1295–1298.
  • Lee SS, Buters JT, Pineau T, Fernandez-Salguero P, Gonzalez FJ. 1996. Role of CYP2E1 in the hepatotoxicity of acetaminophen. J Biol Chem. 271:12063–12067.
  • Li Y, Wang EJ, Chen L, Stein AP, Reuhl KR, Yang CS. 1997. Effects of phenethyl isothiocyanate on acetaminophen metabolism and hepatotoxicity in mice. Toxicol Appl Pharmacol. 144:306–314.
  • Lieber CS. 1997. Cytochrome P-4502E1: its physiological and pathological role. Physiol Rev. 77:517–544.
  • Liu W, Zhou L, Wang H, Zheng B, Wu D, Yang X, Liu J. 2014. CYP2E1 gene rs6413420 polymorphism was first found in the Bouyei ethnic group of China. Int J Clin Exp Med. 7:3612–3620.
  • Lu Y, Cederbaum AI. 2006. Cisplatin-induced hepatotoxicity is enhanced by elevated expression of cytochrome P450 2E1. Toxicol Sci. 89:515–523.
  • Lu Y, Cederbaum AI. 2015. Autophagy protects against CYP2E1/chronic ethanol-induced hepatotoxicity. Biomolecules. 5:2659–2674.
  • Lu Y, Cederbaum AI. 2018. Cytochrome P450s and alcoholic liver disease. CPD. 24:1502–1517.
  • Madias NE, Harrington JT. 1978. Platinum nephrotoxicity. Am J Med. 65:307–314.
  • Martinez-Gil N, Flores-Bellver M, Atienzar-Aroca S, Lopez-Malo D, Urdaneta AC, Sancho-Pelluz J, Peris-Martinez C, Bonet-Ponce L, Romero FJ, Barcia JM. 2015. CYP2E1 in the human retinal pigment epithelium: expression, activity, and induction by ethanol. Invest Ophthalmol Vis Sci. 56:6855–6863.
  • Matsumoto H, Fukui Y. 2002. Pharmacokinetics of ethanol: a review of the methodology. Addict Biol. 7:5–14.
  • McGill MR, Jaeschke H. 2013. Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm Res. 30:2174–2187.
  • Molina-Ortiz D, Camacho-Carranza R, Gonzalez-Zamora JF, Shalkow-Kalincovstein J, Cardenas CR, Nosti-Palacios R, Vences MA. 2014. Differential expression of cytochrome P450 enzymes in normal and tumor tissues from childhood rhabdomyosarcoma. PLoS One. 9:e93261.
  • Monostory K, Hazai E, Vereczkey L. 2004. Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors. Chem-Biol Interact. 147:331–340.
  • Neafsey P, Ginsberg G, Hattis D, Johns DO, Guyton KZ, Sonawane B. 2009. Genetic polymorphism in CYP2E1: population distribution of CYP2E1 activity. J Toxicol Environ Health *Part B Crit Rev. 12:362–388.
  • Nelson DR, Koymans L, Kamataki T, Stegeman JJ, Feyereisen R, Waxman DJ, Waterman MR, Gotoh O, Coon MJ, Estabrook RW, et al. 1996. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics. 6:1–42.
  • Nelson SD, Mitchell JR, Timbrell JA, Snodgrass WR, Corcoran GB 3rd. 1976. Isoniazid and iproniazid: activation of metabolites to toxic intermediates in man and rat. Science. 193:901–903.
  • Neuhaus T, Ko YD, Lorenzen K, Fronhoffs S, Harth V, Brode P, Vetter H, Bolt HM, Pesch B, Bruning T. 2004. Association of cytochrome P450 2E1 polymorphisms and head and neck squamous cell cancer. Toxicol Lett. 151:273–282.
  • Park HJ, Choi YJ, Kim JW, Chun HS, Im I, Yoon S, Han YM, Song CW, Kim H. 2015. Differences in the epigenetic regulation of cytochrome P450 genes between human embryonic stem cell-derived hepatocytes and primary hepatocytes. PLoS One. 10:e0132992.
  • Park WJ, Kim SY, Kim YR, Park JW. 2016. Bortezomib alleviates drug-induced liver injury by regulating CYP2E1 gene transcription. Int J Mol Med. 37:613–622.
  • Park KS, Sohn DH, Veech RL, Song BJ. 1993. Translational activation of ethanol-inducible cytochrome P450 (CYP2E1) by isoniazid. Eur J Pharmacol. 248:7–14.
  • Penaloza CG, Estevez B, Han DM, Norouzi M, Lockshin RA, Zakeri Z. 2014. Sex-dependent regulation of cytochrome P450 family members Cyp1a1, Cyp2e1, and Cyp7b1 by methylation of DNA. FASEB J. 28:966–977.
  • Peter R, Boecker R, Beaune PH, Iwasaki M, Guengerich FP, Yang CS. 1990. Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P-450IIE1. Chem Res Toxicol. 3:566–573.
  • Rahman MA, Gong Y, Kumar S. 2018. In vitro evaluation of structural analogs of diallyl sulfide as novel CYP2E1 inhibitors for their protective effect against xenobiotic-induced toxicity and HIV replication. Toxicol Lett. 292:31–38.
  • Rahman MA, Midde NM, Wu X, Li W, Kumar S. 2017. Kinetic characterizations of diallyl sulfide analogs for their novel role as CYP2E1 enzyme inhibitors. Pharmacol Res Perspect. 5:e00362.
  • Rahman MA, Kodidela S, Sinha N, Haque S, Shukla PK, Rao R, Kumar S. 2019. Plasma exosomes exacerbate alcohol- and acetaminophen-induced toxicity via CYP2E1 pathway. Sci Rep. 9:6571.
  • Rao PS, Midde NM, Miller DD, Chauhan S, Kumar A, Kumar S. 2015. Diallyl sulfide: potential use in novel therapeutic interventions in alcohol, drugs, and disease mediated cellular toxicity by targeting cytochrome P450 2E1. CDM. 16:486–503.
  • Raucy JL, Kraner JC, Lasker JM. 1993. Bioactivation of halogenated hydrocarbons by cytochrome P4502E1. Crit Rev Toxicol. 23:1–20.
  • Raza H, Prabu SK, Robin MA, Avadhani NG. 2004. Elevated mitochondrial cytochrome P450 2E1 and glutathione S-transferase A4-4 in streptozotocin-induced diabetic rats: tissue-specific variations and roles in oxidative stress. Diabetes. 53:185–194.
  • Ronis MJ, Huang J, Crouch J, Mercado C, Irby D, Valentine CR, Lumpkin CK, Ingelman-Sundberg M, Badger TM. 1993. Cytochrome P450 CYP 2E1 induction during chronic alcohol exposure occurs by a two-step mechanism associated with blood alcohol concentrations in rats. J Pharmacol Exp Therapeutics. 264:944–950.
  • Ronis MJ, Johansson I, Hultenby K, Lagercrantz J, Glaumann H, Ingelman-Sundberg M. 1991. Acetone-regulated synthesis and degradation of cytochrome P450E1 and cytochrome P4502B1 in rat liver [corrected]. Eur J Biochem. 198:383–389.
  • Saldana-Ruiz S, Soler-Martin C, Llorens J. 2012. Role of CYP2E1-mediated metabolism in the acute and vestibular toxicities of nineteen nitriles in the mouse. Toxicol Lett. 208:125–132.
  • Shahriary GM, Galehdari H, Jalali A, Zanganeh F, Alavi SM, Aghanoori MR. 2012. CYP2E1*5B, CYP2E1*6, CYP2E1*7B, CYP2E1*2, and CYP2E1*3 allele frequencies in Iranian populations. Asian Pac J Cancer Prev. 13:6505–6510.
  • Sharer JE, Shipley LA, Vandenbranden MR, Binkley SN, Wrighton SA. 1995. Comparisons of phase I and phase II in vitro hepatic enzyme activities of human, dog, rhesus monkey, and cynomolgus monkey. Drug Metabol Disposition. 23:1231–1241.
  • Shimada T, Tsumura F, Yamazaki H. 1999. Prediction of human liver microsomal oxidations of 7-ethoxycoumarin and chlorzoxazone with kinetic parameters of recombinant cytochrome P-450 enzymes. Drug Metabol Disposition. 27:1274–1280.
  • Simi A, Ingelman-Sundberg M. 1999. Post-translational inhibition of cytochrome P-450 2E1 expression by chlomethiazole in Fao hepatoma cells. J Pharmacol Exp Therapeutics. 289:847–852.
  • Spatzenegger M, Liu H, Wang Q, Debarber A, Koop DR, Halpert JR. 2003. Analysis of differential substrate selectivities of CYP2B6 and CYP2E1 by site-directed mutagenesis and molecular modeling. J Pharmacol Exp Ther. 304:477–487.
  • Su XL, Bin B, Cui HW, Ran MR. 2011. Cytochrome P450 2E1 RsaI/PstI and DraI polymorphisms are risk factors for lung cancer in Mongolian and Han Population in Inner Mongolia. Chin J Cancer Res. 23:107–111.
  • Swaminathan K, Kumar SM, Clemens DL, Dey A. 2013. Inhibition of CYP2E1 leads to decreased advanced glycated end product formation in high glucose treated ADH and CYP2E1 over-expressing VL-17A cells. Biochim Biophys Acta. 1830:4407–4416.
  • Teixeira RL, Morato RG, Cabello PH, Muniz LM, Moreira Ada S, Kritski AL, Mello FC, Suffys PN, Miranda AB, Santos AR. 2011. Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients. Mem Inst Oswaldo Cruz. 106:716–724.
  • Terelius Y, Ingelman-Sundberg M. 1986. Metabolism of n-pentane by ethanol-inducible cytochrome P-450 in liver microsomes and reconstituted membranes. Eur J Biochem. 161:303–308.
  • Trafalis DT, Panteli ES, Grivas A, Tsigris C, Karamanakos PN. 2010. CYP2E1 and risk of chemically mediated cancers. Expert Opin Drug Metab Toxicol. 6:307–319.
  • Uchimoto T, Itoga S, Nezu M, Sunaga M, Tomonaga T, Nomura F. 2007. Role of the genetic polymorphisms in the 5'-flanking region for transcriptional regulation of the human CYP2E1 gene. Alcohol Clin Exp Res. 31:S36–S42.
  • Ueshima Y, Tsutsumi M, Takase S, Matsuda Y, Kawahara H. 1996. Acetaminophen metabolism in patients with different cytochrome P-4502E1 genotypes. Alcoholism Clin Exp Res. 20:25a–28a.
  • Ulusoy G, Arinc E, Adali O. 2007. Genotype and allele frequencies of polymorphic CYP2E1 in the Turkish population. Arch Toxicol. 81:711–718.
  • Vieira I, Sonnier M, Cresteil T. 1996. Developmental expression of CYP2E1 in the human liver. Hypermethylation control of gene expression during the neonatal period. Eur J Biochem. 238:476–483.
  • Wallace MC, Hamesch K, Lunova M, Kim Y, Weiskirchen R, Strnad P, Friedman SL. 2015. Standard operating procedures in experimental liver research: thioacetamide model in mice and rats. Lab Anim. 49:21–29.
  • Wang S, Bott D, Tung A, Sugamori KS, Grant DM. 2015a. Relative contributions of CYP1A2 and CYP2E1 to the bioactivation and clearance of 4-aminobiphenyl in adult mice. Drug Metab Dispos. 43:916–921.
  • Wang J, Hu Y, Nekvindova J, Ingelman-Sundberg M, Neve EP. 2010. IL-4-mediated transcriptional regulation of human CYP2E1 by two independent signaling pathways. Biochem Pharmacol. 80:1592–1600.
  • Wang T, Shankar K, Ronis MJ, Mehendale HM. 2000. Potentiation of thioacetamide liver injury in diabetic rats is due to induced CYP2E1. J Pharmacol Exp Therapeutics. 294:473–479.
  • Wang S, Sugamori KS, Tung A, McPherson JP, Grant DM. 2015b. N-hydroxylation of 4-aminobiphenyl by CYP2E1 produces oxidative stress in a mouse model of chemically induced liver cancer. Toxicol Sci. 144:393–405.
  • Wang Y, Yu D, Tolleson WH, Yu L-R, Green B, Zeng L, Chen Y, Chen S, Ren Z, Guo L, et al. 2017. A systematic evaluation of microRNAs in regulating human hepatic CYP2E1. Biochem Pharmacol. 138:174–184.
  • Wauthier V, Schenten V, Verbeeck RK, Calderon PB. 2006. Ageing is associated with increased expression but decreased activity of CYP2E1 in male Wistar rats. Life Sci. 79:1913–1920.
  • Weber LW, Boll M, Stampfl A. 2003. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol. 33:105–136.
  • Wenker MA, Kezic S, Monster AC, de Wolff FA. 2001. Metabolic capacity and interindividual variation in toxicokinetics of styrene in volunteers. Hum Exp Toxicol. 20:221–228.
  • Wilby MJ, Hutchinson PJ. 2004. The pharmacology of chlormethiazole: a potential neuroprotective agent? CNS Drug Rev. 10:281–294.
  • Woodcroft KJ, Hafner MS, Novak RF. 2002. Insulin signaling in the transcriptional and posttranscriptional regulation of CYP2E1 expression. Hepatology. 35:263–273.
  • Wu YS, Salmela KS, Lieber CS. 1998. Microsomal acetaldehyde oxidation is negligible in the presence of ethanol. Alcohol Clin Exp Res. 22:1165–1169.
  • Xu L, Yang M, Zhao T, Jin H, Xu Z, Li M, Chen H. 2014. The polymorphism of CYP2E1 Rsa I/Pst I gene and susceptibility to respiratory system cancer: a systematic review and meta-analysis of 34 studies. Medicine. 93:e178.
  • Yamamura Y, Koyama N, Umehara K. 2015. Comprehensive kinetic analysis and influence of reaction components for chlorzoxazone 6-hydroxylation in human liver microsomes with CYP antibodies. Xenobiotica. 45:353–360.
  • Yamazaki H, Nakano M, Gillam EM, Bell LC, Guengerich FP, Shimada T. 1996. Requirements for cytochrome b5 in the oxidation of 7-ethoxycoumarin, chlorzoxazone, aniline, and N-nitrosodimethylamine by recombinant cytochrome P450 2E1 and by human liver microsomes. Biochem Pharmacol. 52:301–309.
  • Yamazoe Y, Ito K, Yoshinari K. 2011. Construction of a CYP2E1-template system for prediction of the metabolism on both site and preference order. Drug Metab Rev. 43:409–439.
  • Yang CS, Chhabra SK, Hong JY, Smith TJ. 2001. Mechanisms of inhibition of chemical toxicity and carcinogenesis by diallyl sulfide (DAS) and related compounds from garlic. J Nutr. 131:1041S–1045S.
  • Yin X, Xiong W, Wang Y, Tang W, Xi W, Qian S, Guo Y. 2018. Association of CYP2E1 gene polymorphisms with bladder cancer risk: a systematic review and meta-analysis. Medicine. 97:e11910.
  • Yoon M, Madden MC, Barton HA. 2007. Extrahepatic metabolism by CYP2E1 in PBPK modeling of lipophilic volatile organic chemicals: impacts on metabolic parameter estimation and prediction of dose metrics. J Toxicol Environ Health Part A. 70:1527–1541.
  • Zanger UM, Schwab M. 2013. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 138:103–141.
  • Zhang T, Xiang CD, Gale D, Carreiro S, Wu EY, Zhang EY. 2008. Drug transporter and cytochrome P450 mRNA expression in human ocular barriers: implications for ocular drug disposition. Drug Metab Dispos. 36:1300–1307.
  • Zhong Y, Dong G, Luo H, Cao J, Wang C, Wu J, Feng YQ, Yue J. 2012. Induction of brain CYP2E1 by chronic ethanol treatment and related oxidative stress in hippocampus, cerebellum, and brainstem. Toxicology. 302:275–284.
  • Zhong XB, Leeder JS. 2013. Epigenetic regulation of ADME-related genes: focus on drug metabolism and transport. Drug Metab Dispos. 41:1721–1724.
  • Zhong S, Han W, Hou C, Liu J, Wu L, Liu M, Liang Z, Lin H, Zhou L, Liu S, et al. 2017. Relation of transcriptional factors to the expression and activity of cytochrome P450 and UDP-glucuronosyltransferases 1A in human liver: co-expression network analysis. Aaps J. 19:203–214.
  • Zimmerman HJ, Maddrey WC. 1995. Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure. Hepatology. 22:767–773.
  • Zuber R, Anzenbacherova E, Anzenbacher P. 2002. Cytochromes P450 and experimental models of drug metabolism. J Cell Mol Med. 6:189–198.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.