{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T18:57:17Z","timestamp":1782845837975,"version":"3.54.5"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T00:00:00Z","timestamp":1653264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005916","name":"Universidad de La Frontera","doi-asserted-by":"publisher","award":["DI22\u20130007"],"award-info":[{"award-number":["DI22\u20130007"]}],"id":[{"id":"10.13039\/501100005916","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Programa de Formaci\u00f3n de Investigadores Postdoctorales 2022","award":["DI22\u20130007"],"award-info":[{"award-number":["DI22\u20130007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>One of the key routes through which ethanol induces oxidative stress appears to be the activation of cytochrome P450 2E1 at different levels of ethanol intake. Our aim was to determine if oral \u03b2-carotene intake had an antioxidant effect on CYP2E1 gene expression in mice that had previously consumed ethanol. C57BL\/6 mice were used and distributed into: control (C), low-dose alcohol (LA), moderate-dose alcohol (MA), \u03b2-carotene (B), low-dose alcohol+\u03b2-carotene (LA + B), and moderate-dose alcohol+\u03b2-carotene (MA + B). Animals were euthanized at the end of the experiment, and liver tissue was taken from each one. CYP2E1 was measured using qPCR to detect liver damage. The relative expression level of each RNA was estimated using the comparative threshold cycle (Ct) technique (2\u2212\u0394\u0394CT method) by averaging the Ct values from three replicates. The LA+B (2267 \u00b1 0.707) and MA+B (2.307 \u00b1 0.384) groups had the highest CYP2E1 fold change values. On the other hand, the C (1.053 \u00b1 0.292) and LA (1.240 \u00b1 0.163) groups had the lowest levels. These results suggest that ethanol feeding produced a fold increase in CYP2E1 protein in mice as compared to the control group. Increased CYP2E1 activity was found to support the hypothesis that \u03b2-carotene might be dangerous during ethanol exposure in animal models. Our findings imply that \u03b2-carotene can increase the hepatic damage caused by low and high doses of alcohol. Therefore, the quantity of alcohol ingested, the exposure period, the regulatory mechanisms of alcoholic liver damage, and the signaling pathways involved in the consumption of both alcohol and antioxidant must all be considered.<\/jats:p>","DOI":"10.3390\/antiox11051033","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T22:57:22Z","timestamp":1653346642000},"page":"1033","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["\u03b2-Carotene Increases Activity of Cytochrome P450 2E1 during Ethanol Consumption"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3184-6482","authenticated-orcid":false,"given":"Cristian","family":"Sandoval","sequence":"first","affiliation":[{"name":"Escuela de Tecnolog\u00eda M\u00e9dica, Facultad de Salud, Universidad Santo Tom\u00e1s, Los Carreras 753, Osorno 5310431, Chile"},{"name":"Departamento de Ingenier\u00eda Qu\u00edmica, Facultad de Ingenier\u00eda y Ciencias, Universidad de La Frontera, Temuco 4811230, Chile"},{"name":"Departamento de Ciencias Precl\u00ednicas, Facultad de Medicina, Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Mella","sequence":"additional","affiliation":[{"name":"Carrera de Tecnolog\u00eda M\u00e9dica, Facultad de Medicina, Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Godoy","sequence":"additional","affiliation":[{"name":"N\u00facleo Cient\u00edfico y Tecnol\u00f3gico en Biorecursos (BIOREN), Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khosrow","family":"Adeli","sequence":"additional","affiliation":[{"name":"Molecular Medicine, Research Institute The Hospital for Sick Children University of Toronto, Toronto, ON M5G 1X8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Far\u00edas","sequence":"additional","affiliation":[{"name":"Departamento de Ingenier\u00eda Qu\u00edmica, Facultad de Ingenier\u00eda y Ciencias, Universidad de La Frontera, Temuco 4811230, Chile"},{"name":"N\u00facleo Cient\u00edfico y Tecnol\u00f3gico en Biorecursos (BIOREN), Universidad de La Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1159\/000077608","article-title":"Non-oxidative Metabolism of Ethanol by Rat Pancreatic Acini","volume":"4","author":"Haber","year":"2004","journal-title":"Pancreatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.3390\/ijerph7041540","article-title":"Ethanol and Cognition: Indirect Effects, Neurotoxicity, and Neuroprotection: A Review","volume":"7","author":"Brust","year":"2010","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"ref_3","unstructured":"World Health Organization (2011). Alcohol. Descriptive Note N\u00ba 349."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1111\/j.1440-1746.2006.04595.x","article-title":"Cytochrome P450 2E1-dependent Oxidant Stress and Upregulation of Anti-oxidant Defense in Liver Cells","volume":"21","author":"Cederbaum","year":"2006","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1002\/hep.22837","article-title":"Exogenous Thioredoxin Prevents Ethanol-induced Oxidative Damage and Apoptosis in Mouse Liver","volume":"49","author":"Cohen","year":"2009","journal-title":"Hepatology"},{"key":"ref_6","first-page":"3","article-title":"Alcoholismo y sociedad, tendencias actuales","volume":"33","year":"2004","journal-title":"Rev. Cub. Med. Mil."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"138","DOI":"10.15332\/s1794-9998.2005.0002.02","article-title":"Reacciones fisiol\u00f3gicas y neuroqu\u00edmicas del alcoholismo","volume":"1","author":"Arias","year":"2005","journal-title":"Diversitas"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1097\/01.alc.0000179379.03078.8f","article-title":"Use of CYP2E1-transfected Human Liver Cell Lines in Elucidating the Actions of Ethanol","volume":"29","author":"Lakshman","year":"2006","journal-title":"Alcohol Clin. Exp. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.taap.2006.05.003","article-title":"Metabolic Basis of Ethanol-induced Cytotoxicity in Recombinant HepG2 Cells: Role of Nonoxidative Metabolism","volume":"216","author":"Wu","year":"2006","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.freeradbiomed.2007.11.004","article-title":"CYP2E1 and Oxidative Liver Injury by Alcohol","volume":"44","author":"Lu","year":"2008","journal-title":"Free Rad. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/ncb0910-814","article-title":"Eaten Alive: A History of Macroautophagy","volume":"12","author":"Yang","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0891-5849(01)00769-9","article-title":"Contribution of Mitochondria to Oxidative Stress Associated with Alcoholic Liver Disease","volume":"32","author":"Bailey","year":"2002","journal-title":"Free Rad. Biol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1053\/gast.2002.33613","article-title":"Alcohol and Mitochondria: A Dysfunctional Relationship","volume":"122","author":"Hoek","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_14","first-page":"285","article-title":"Dangerous Byproducts of Alcohol Breakdown: Focus on Adducts","volume":"27","author":"Tuma","year":"2003","journal-title":"Alcohol Res. Health"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"942","DOI":"10.4067\/S0717-95022017000300024","article-title":"Ethanol Intake and Toxicity: In Search of New Treatments","volume":"35","author":"Sandoval","year":"2017","journal-title":"Int. J. Morphol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.redox.2014.09.004","article-title":"Regulation of the Effects of CYP2E1-induced Oxidative Stress by JNK Signaling","volume":"3","author":"Schattenberg","year":"2014","journal-title":"Redox Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Diesinger, T., Buko, V., Lautwein, A., Dvorsky, R., Belonovskaya, E., Lukivskaya, O., Naruta, E., Kirko, S., Andreev, V., and Buckert, D. (2020). Drug Targeting CYP2E1 for the Treatment of Early-stage Alcoholic Steatohepatitis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0235990"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0891-5849(02)00905-X","article-title":"Superoxide Dismutase Multigene Family: A Comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) Gene Structures, Evolution, and Expression","volume":"33","author":"Zelko","year":"2002","journal-title":"Free Rad. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.brainres.2005.09.032","article-title":"Marked Differences in the Efficacy of Post-insult Gene Therapy with Catalase versus Glutathione Peroxidase","volume":"1063","author":"Chang","year":"2005","journal-title":"Brain Res."},{"key":"ref_20","first-page":"1713","article-title":"Morphoquantitative Effects of Oral \u03b2-carotene Supplementation on Liver of C57BL\/6 Mice Exposed to Ethanol Consumption","volume":"12","author":"Sandoval","year":"2019","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11815","DOI":"10.1074\/jbc.M117.777748","article-title":"\u03b2-Adrenergic Induction of Lipolysis in Hepatocytes Is Inhibited by Ethanol Exposure","volume":"292","author":"Schott","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1556\/650.2020.31834","article-title":"A M\u00e1jbetegs\u00e9gek Kialakul\u00e1s\u00e1nak \u00daj Szempontjai\u2014K\u00fcl\u00f6n\u00f6s Tekintettel Az Autophagi\u00e1ra \u00c8s A mikro-RNS Szerep\u00e9re","volume":"161","author":"Werling","year":"2020","journal-title":"Orvosi Hetilap"},{"key":"ref_23","unstructured":"Committee for the Update of the Guide for the Care and Use of Laboratory Animals, Institute for Laboratory Animal Research, and Division on Earth and Life Studies (2011). Guide for the Care and Use of Laboratory Animals, The National Academies Press. [8th ed.]."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1590\/S0100-879X2003000100017","article-title":"Low ethanol consumption increases insulin sensitivity in Wistar rats","volume":"36","author":"Furuya","year":"2003","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_25","first-page":"132","article-title":"The antiapoptotic effects of different doses of \u03b2-carotene in chronic ethanol-fed rats","volume":"2","author":"Peng","year":"2013","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13128","DOI":"10.18632\/aging.103401","article-title":"Long-term low-dose ethanol intake improves healthspan and resists high-fat diet-induced obesity in mice","volume":"12","author":"Diao","year":"2020","journal-title":"Aging"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"pdb.prot5439","DOI":"10.1101\/pdb.prot5439","article-title":"Purification of RNA Using TRIzol (TRI Reagent)","volume":"2010","author":"Rio","year":"2010","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_28","first-page":"194","article-title":"Multi-perspective quality control of Illumina RNA sequencing data analysis","volume":"16","author":"Sheng","year":"2017","journal-title":"Brief. Funct. Genom."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1677\/jme.0.0290023","article-title":"Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): Trends and problems","volume":"29","author":"Bustin","year":"2002","journal-title":"J. Mol. Endocrinol."},{"key":"ref_31","unstructured":"Pfaffl, M.W. (2004). Quantification Strategies in Real-Time PCR. A-Z of Quantitative PCR, International University Line."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1002\/art.21641","article-title":"Analysis of pigmented villonodular synovitis with genome-wide complementary DNA microarray and tissue array technology reveals insight into potential novel therapeutic approaches","volume":"54","author":"Finis","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real time quantification PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1097\/00019606-200603000-00009","article-title":"Validation of the 2-DeltaDeltaCt calculation as an alternate method of data analysis for quantitative PCR of BCR-ABL P210 transcripts","volume":"15","author":"Arocho","year":"2006","journal-title":"Diagn. Mol. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/ijc.10937","article-title":"CYP Enzyme Polymorph\u0131sms and Suscept\u0131b\u0131l\u0131ty to HCV-Related Chron\u0131c Liver Disease and Liver Cancer","volume":"104","author":"Silvestri","year":"2003","journal-title":"Int. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1081\/DMR-200033441","article-title":"The Discovery of the Microsomal Ethanol Oxidizing System and Its Physiologic and Pathologic Role","volume":"36","author":"Lieber","year":"2004","journal-title":"Drug Metab. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"367","DOI":"10.4067\/S0717-95022018000100367","article-title":"Rol del consumo de alcohol y antioxidantes sobre la metilaci\u00f3n global del ADN y c\u00e1ncer","volume":"36","author":"Sandoval","year":"2018","journal-title":"Int. J. Morphol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1080\/10942912.2021.1961801","article-title":"Effectiveness of antioxidant treatments on cytochrome P450 2E1 (CYP2E1) activity after alcohol exposure in humans and in vitro models: A systematic review","volume":"24","author":"Carrasco","year":"2021","journal-title":"Int. J. Food Prop."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"285","DOI":"10.17576\/jsm-2022-5101-23","article-title":"Oral supplementation of b-carotene benefits the hepatic structure and metabolism in mice exposed to chronic ethanol consumption","volume":"51","author":"Sandoval","year":"2022","journal-title":"Sains Malays."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1002\/hep.510300413","article-title":"Induction of cytochrome P450 enzymes and generation of protein-aldehyde adducts are associated with sex-dependent sensitivity to alcohol-induced liver disease in micropigs","volume":"30","author":"Parkkila","year":"1999","journal-title":"Hepatology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1002\/hep.20673","article-title":"Activity of CYP2E1 and CYP3A enzymes in adults with moderate alcohol consumption: A comparison with nonalcoholics","volume":"41","author":"Liangpunsakul","year":"2005","journal-title":"Hepatology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/toxsci\/kfj031","article-title":"Cisplatin-Induced Hepatotoxicity Is Enhanced by Elevated Expression of Cytochrome P450 2E1","volume":"89","author":"Lu","year":"2006","journal-title":"Tox\u0131col. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/cbf.1579","article-title":"Effects of beta-carotene on antioxidant status in rats with chronic alcohol consumption","volume":"27","author":"Lin","year":"2009","journal-title":"Cell Biochem. Funct."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Sandoval, C., Far\u00edas, J., Zamorano, M., and Herrera, C. (2022). Vitamin Supplements as a Nutritional Strategy against Chronic Alcohol Consumption? An Updated Review. Antioxidants, 11.","DOI":"10.37247\/PAB.1.22.12"},{"key":"ref_45","first-page":"944","article-title":"Cytochrome P450 CYP 2E1 induction during chronic alcohol exposure occurs by a two-step mechanism associated with blood alcohol concentrations in rats","volume":"264","author":"Ronis","year":"1993","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/0006-291X(88)90539-6","article-title":"Ligand-dependent maintenance of ethanol-inducible cytochrome P-450 in primary rat hepatocyte cell cultures","volume":"150","author":"Eliasson","year":"1988","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_47","first-page":"991","article-title":"Microsomal ethanol-oxidizing system (MEOS): The first 30 years (1968\u20131998)\u2014A review","volume":"23","author":"Lieber","year":"1999","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1093\/jn\/119.1.116","article-title":"A review of epidemiologic evidence that carotenoids reduce the risk of cancer","volume":"119","author":"Ziegler","year":"1989","journal-title":"J. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"251S","DOI":"10.1093\/ajcn\/53.1.251S","article-title":"Vegetables, fruits, and carotenoids and the risk of cancer","volume":"53","author":"Ziegler","year":"1991","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"265S","DOI":"10.1093\/ajcn\/53.1.265S","article-title":"B-carotene and cancer prevention: The Base1 Study","volume":"53","author":"Stahelin","year":"1991","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_51","first-page":"443","article-title":"Vitamin A, @-carotene, and the risk of cancer: A prospective study","volume":"79","author":"Chao","year":"1987","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1002\/hep.1840150522","article-title":"Interaction of ethanol with beta-carotene: Delayed blood clearance and enhanced hepatotoxicity","volume":"15","author":"Leo","year":"1992","journal-title":"Hepatology"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/5\/1033\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:17:15Z","timestamp":1760138235000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/5\/1033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,23]]},"references-count":52,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["antiox11051033"],"URL":"https:\/\/doi.org\/10.3390\/antiox11051033","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,23]]}}}