{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T01:55:00Z","timestamp":1788400500543,"version":"build-2803163510"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Alcohol-associated liver disease (ALD) increases the health burden worldwide, but effective drugs to prevent ALD are lacking. Furfural is a small molecule that can limit alcohol production in microorganisms and may have the capacity to attenuate ethanol-induced toxicity.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Human HepG2 cells were incubated with ethanol and furfural, and cell viability, NAD<jats:sup>+<\/jats:sup>\/NADH ratio, and mitochondrial function assays were performed. RNA sequencing (RNA-seq) data were used to annotate enriched pathways, and these findings were confirmed by reverse transcription-quantitative PCR (RT\u2013qPCR) and Western blotting. C57BL\/6J mice were fed a Lieber-DeCarli liquid diet. After 4\u00a0weeks, biochemical analysis of mouse serum and histological analysis of mouse livers were performed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Different concentrations of furfural exerted different effects on mitochondria: low-dose furfural reduced reactive oxygen species (ROS) production, maintained mitochondrial transmembrane potential, and inhibited apoptosis pathway activation, while high-dose furfural led to the opposite effects. In mice, furfural mitigated transaminase increases and attenuated the lipid metabolism disorder that had been induced by ethanol.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Low-dose furfural reduced ethanol-induced toxicity in the liver. Consuming food or beverages containing the appropriate level of furfural when drinking alcohol may be a convenient and useful way to prevent ALD.<\/jats:p>","DOI":"10.3389\/fphar.2022.906933","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T07:36:06Z","timestamp":1654673766000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Furfural Produces Dose-Dependent Attenuating Effects on Ethanol-Induced Toxicity in the Liver"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhuo","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanmei","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiue","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.microc.2005.06.005","article-title":"HPLC Determination of 2-furaldehyde and 5-Hydroxymethyl-2-Furaldehyde in Alcoholic Beverages","volume":"82","author":"Alc\u00e1zar","year":"2006","journal-title":"Microchem. J."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00592-010-0227-z","article-title":"The IGF System","volume":"48","author":"Annunziata","year":"2011","journal-title":"Acta Diabetol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/1754-6834-6-22","article-title":"The Influence of HMF and Furfural on Redox-Balance and Energy-State of Xylose-Utilizing Saccharomyces cerevisiae","volume":"6","author":"Ask","year":"2013","journal-title":"Biotechnol. Biofuels"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.jhep.2014.12.005","article-title":"Alcohol Drinking Pattern and Risk of Alcoholic Liver Cirrhosis: a Prospective Cohort Study","volume":"62","author":"Askgaard","year":"2015","journal-title":"J. Hepatol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.biortech.2011.10.060","article-title":"Effect of Lignin-Derived and Furan Compounds Found in Lignocellulosic Hydrolysates on Biomethane Production","volume":"104","author":"Barakat","year":"2012","journal-title":"Bioresour. Technol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1053\/jhep.2002.32101","article-title":"Lower Risk for Alcohol-Induced Cirrhosis in Wine Drinkers","volume":"35","author":"Becker","year":"2002","journal-title":"Hepatology"},{"key":"B7","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.cmet.2019.02.011","article-title":"Mitochondria Bound to Lipid Droplets: Where Mitochondrial Dynamics Regulate Lipid Storage and Utilization","volume":"29","author":"Benador","year":"2019","journal-title":"Cell Metab."},{"key":"B8","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1007\/s11883-012-0230-7","article-title":"Effects of Ethanol Intake on Lipoproteins","volume":"14","author":"Brinton","year":"2012","journal-title":"Curr. Atheroscler. Rep."},{"key":"B9","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.cld.2012.08.002","article-title":"Alcohol Metabolism","volume":"16","author":"Cederbaum","year":"2012","journal-title":"Clin. Liver Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1080\/19393210.2014.981601","article-title":"Furanic Compounds and Furfural in Different Coffee Products by Headspace Liquid-phase Micro-extraction Followed by Gas Chromatography-Mass Spectrometry: Survey and Effect of Brewing Procedures","volume":"8","author":"Chaichi","year":"2015","journal-title":"Food Addit. Contam. Part B Surveill."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1250684","DOI":"10.1126\/science.1250684","article-title":"mTOR- and HIF-1\u03b1-Mediated Aerobic Glycolysis as Metabolic Basis for Trained Immunity","volume":"345","author":"Cheng","year":"2014","journal-title":"Science"},{"key":"B12","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.tem.2010.06.005","article-title":"Insulin Signaling Meets Mitochondria in Metabolism","volume":"21","author":"Cheng","year":"2010","journal-title":"Trends Endocrinol. Metab."},{"key":"B13","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/s0163-7827(01)00024-8","article-title":"Control of Mitochondrial Beta-Oxidation Flux","volume":"41","author":"Eaton","year":"2002","journal-title":"Prog. Lipid Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1056\/NEJMra1715733","article-title":"Alcohol Use in Patients with Chronic Liver Disease","volume":"379","author":"Fuster","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1002\/hep.27054","article-title":"Coffee, Alcohol and Other Beverages in Relation to Cirrhosis Mortality: the Singapore Chinese Health Study","volume":"60","author":"Goh","year":"2014","journal-title":"Hepatology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41574-018-0096-z","article-title":"The Role of Hypoxia-Inducible Factors in Metabolic Diseases","volume":"15","author":"Gonzalez","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/S0140-6736(18)31310-2","article-title":"Alcohol Use and Burden for 195 Countries and Territories, 1990-2016: a Systematic Analysis for the Global Burden of Disease Study 2016","volume":"392","author":"Griswold","year":"2018","journal-title":"Lancet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"42165","DOI":"10.1074\/jbc.M112.377374","article-title":"Dynamic Adaptation of Liver Mitochondria to Chronic Alcohol Feeding in Mice: Biogenesis, Remodeling, and Functional Alterations","volume":"287","author":"Han","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B19","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3177\/jnsv.63.35","article-title":"5-HMF Attenuates Liver Fibrosis in CCl4-Plus-Alcohol-Induced Mice by Suppression of Oxidative Stress","volume":"63","author":"Han","year":"2017","journal-title":"J. Nutr. Sci. Vitaminol. (Tokyo)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1159\/000485089","article-title":"Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species","volume":"44","author":"He","year":"2017","journal-title":"Cell Physiol. Biochem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nature08778","article-title":"SIRT3 Regulates Mitochondrial Fatty-Acid Oxidation by Reversible Enzyme Deacetylation","volume":"464","author":"Hirschey","year":"2010","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1016\/j.cmet.2020.10.010","article-title":"TANK-binding Kinase 1 Regulates the Localization of Acyl-CoA Synthetase ACSL1 to Control Hepatic Fatty Acid Oxidation","volume":"32","author":"Huh","year":"2020","journal-title":"Cell Metab."},{"key":"B23","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1111\/add.14873","article-title":"Problem Drinking, Wellbeing and Mortality Risk in Chinese Men: Findings from the China Kadoorie Biobank","volume":"115","author":"Im","year":"2020","journal-title":"Addiction"},{"key":"B24","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.tcb.2014.04.002","article-title":"NAD+ and Sirtuins in Aging and Disease","volume":"24","author":"Imai","year":"2014","journal-title":"Trends Cell Biol."},{"key":"B25","volume-title":"Evaluation of Certain Food Additives and Contaminants Forty-First Report of the Joint FAO\/WHO Expert Committee on Food Additives","year":"2004"},{"key":"B26","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s42255-019-0161-5","article-title":"NAD+ Homeostasis in Health and Disease","volume":"2","author":"Katsyuba","year":"2020","journal-title":"Nat. Metab."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1007\/s00253-010-2518-2","article-title":"Transcriptome Shifts in Response to Furfural and Acetic Acid in Saccharomyces cerevisiae","volume":"86","author":"Li","year":"2010","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s00253-006-0567-3","article-title":"Genomic Adaptation of Ethanologenic Yeast to Biomass Conversion Inhibitors","volume":"73","author":"Liu","year":"2006","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1007\/s12010-016-2356-5","article-title":"Effect of Furfural on Saccharomyces Carlsbergensis Growth, Physiology and Ethanol Production","volume":"182","author":"Lopes da Silva","year":"2017","journal-title":"Appl. Biochem. Biotechnol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1038\/nm1052","article-title":"mTOR Inhibition Reverses Akt-dependent Prostate Intraepithelial Neoplasia through Regulation of Apoptotic and HIF-1-dependent Pathways","volume":"10","author":"Majumder","year":"2004","journal-title":"Nat. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"9680","DOI":"10.1039\/d1fo01155c","article-title":"Effect of Roasting Conditions on Cocoa Bioactivity and Gut Microbiota Modulation","volume":"12","author":"Maldonado-Mateus","year":"2021","journal-title":"Food Funct."},{"key":"B32","doi-asserted-by":"publisher","first-page":"4315","DOI":"10.1128\/AEM.00567-09","article-title":"Silencing of NADPH-dependent Oxidoreductase Genes (yqhD and dkgA) in Furfural-Resistant Ethanologenic Escherichia coli","volume":"75","author":"Miller","year":"2009","journal-title":"Appl. Environ. Microbiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.molmet.2016.02.002","article-title":"Thioesterase Superfamily Member 1 Suppresses Cold Thermogenesis by Limiting the Oxidation of Lipid Droplet-Derived Fatty Acids in Brown Adipose Tissue","volume":"5","author":"Okada","year":"2016","journal-title":"Mol. Metab."},{"key":"B34","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/s0168-8278(86)80006-x","article-title":"Histological Course of Alcoholic Hepatitis. Influence of Abstinence, Sex and Extent of Hepatic Damage","volume":"2","author":"Par\u00e9s","year":"1986","journal-title":"J. Hepatol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/0278-6915(94)90086-8","article-title":"Metabolism and Excretion of [14C]furfural in the Rat and Mouse","volume":"32","author":"Parkash","year":"1994","journal-title":"Food Chem. Toxicol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"3852","DOI":"10.1021\/acs.jafc.2c00269","article-title":"5-Hydroxymethylfurfural Exerts Negative Effects on Gastric Mucosal Epithelial Cells by Inducing Oxidative Stress, Apoptosis, and Tight Junction Disruption","volume":"70","author":"Qiu","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.1016\/S0140-6736(09)60746-7","article-title":"Global Burden of Disease and Injury and Economic Cost Attributable to Alcohol Use and Alcohol-Use Disorders","volume":"373","author":"Rehm","year":"2009","journal-title":"Lancet"},{"key":"B38","doi-asserted-by":"publisher","first-page":"4076","DOI":"10.1128\/aem.69.7.4076-4086.2003","article-title":"Effects of Furfural on the Respiratory Metabolism of Saccharomyces cerevisiae in Glucose-Limited Chemostats","volume":"69","author":"S\u00e1rv\u00e1ri Horv\u00e1th","year":"2003","journal-title":"Appl. Environ. Microbiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/j.matbio.2018.04.006","article-title":"Liver Fibrosis: Direct Antifibrotic Agents and Targeted Therapies","author":"Schuppan","year":"2018","journal-title":"Matrix Biol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/ajg.2017.469","article-title":"ACG Clinical Guideline: Alcoholic Liver Disease","volume":"113","author":"Singal","year":"2018","journal-title":"Am. J. Gastroenterol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/0002-8703(87)90614-4","article-title":"Alcohol-induced Changes in Serum Lipoproteins and in Their Metabolism","volume":"113","author":"Taskinen","year":"1987","journal-title":"Am. Heart J."},{"key":"B42","doi-asserted-by":"publisher","first-page":"8675","DOI":"10.1007\/s00253-014-5924-z","article-title":"Detoxification of Furfural in Corynebacterium Glutamicum under Aerobic and Anaerobic Conditions","volume":"98","author":"Tsuge","year":"2014","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"178","DOI":"10.3892\/or.2018.6790","article-title":"Hypoxia Increases Chemoresistance in Human Medulloblastoma DAOY Cells via Hypoxia-inducible F-actor 1\u03b1-mediated D-ownregulation of the CYP2B6, CYP3A4 and CYP3A5 E-nzymes and I-nhibition of C-ell P-roliferation","volume":"41","author":"Valencia-Cervantes","year":"2019","journal-title":"Oncol. Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1002\/bit.10188","article-title":"Furfural, 5-hydroxymethyl Furfural, and Acetoin Act as External Electron Acceptors during Anaerobic Fermentation of Xylose in Recombinant Saccharomyces cerevisiae","volume":"78","author":"Wahlbom","year":"2002","journal-title":"Biotechnol. Bioeng."},{"key":"B45","doi-asserted-by":"publisher","first-page":"5132","DOI":"10.1128\/AEM.05008-11","article-title":"Increased Furfural Tolerance Due to Overexpression of NADH-dependent Oxidoreductase FucO in Escherichia coli Strains Engineered for the Production of Ethanol and Lactate","volume":"77","author":"Wang","year":"2011","journal-title":"Appl. Environ. Microbiol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1007\/s00253-011-3632-5","article-title":"Microbial Degradation of Furanic Compounds: Biochemistry, Genetics, and Impact","volume":"92","author":"Wierckx","year":"2011","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"571","DOI":"10.3748\/wjg.v8.i3.571","article-title":"Epidemiological and Histopathological Study of Relevance of Guizhou Maotai Liquor and Liver Diseases","volume":"8","author":"Wu","year":"2002","journal-title":"World J. Gastroenterol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1089\/ars.2007.1672","article-title":"NAD+\/NADH and NADP+\/NADPH in Cellular Functions and Cell Death: Regulation and Biological Consequences","volume":"10","author":"Ying","year":"2008","journal-title":"Antioxid. Redox Signal"},{"key":"B49","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.freeradbiomed.2021.08.005","article-title":"Activation of PPAR\u03b1-Catalase Pathway Reverses Alcoholic Liver Injury via Upregulating NAD Synthesis and Accelerating Alcohol Clearance","volume":"174","author":"Yue","year":"2021","journal-title":"Free Radic. Biol. Med."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.906933\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T07:36:10Z","timestamp":1654673770000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.906933\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,8]]},"references-count":49,"alternative-id":["10.3389\/fphar.2022.906933"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.906933","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,8]]},"article-number":"906933"}}