{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:35:32Z","timestamp":1792650932883,"version":"4.5.0"},"reference-count":111,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p>With the increasing prevalence of alcohol-related diseases, expanding our understanding of the toxic effects of excessive alcohol consumption is critical for prevention and treatment of metabolic and inflammatory pathology. This review summarizes current knowledge on the metabolic dysfunction and inflammation caused by alcohol and their impact on the pathogenesis of alcohol-related liver disease (ALD), type 2 diabetes, cardiovascular disease, and obesity, and neurological damage. It highlights recent evidence that alcohol induces a cascade of reactive oxygen species (ROS)-mediated lipid peroxidation and nicotinamide adenine dinucleotide (NAD<jats:sup>+<\/jats:sup>) depletion, triggering mitochondrial dysfunction and metabolic imbalances in the liver, heart, pancreas, and brain. By integrating these mechanistic insights with emerging data on how disrupted lipid and glucose metabolism amplify immune dysregulation, the review underscores the interplay between metabolic and inflammatory pathways in exacerbating tissue injury across these organs. A deep understanding of these metabolic and inflammatory disruptions is therefore essential for developing novel therapeutic strategies, including metabolic and nutritional interventions, aimed at mitigating the health risks of excessive alcohol consumption.<\/jats:p>","DOI":"10.3389\/ftox.2025.1670769","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T05:27:13Z","timestamp":1759123633000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":41,"title":["Excessive alcohol consumption: a driver of metabolic dysfunction and inflammation"],"prefix":"10.3389","volume":"7","author":[{"given":"Jaeeun","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Young","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunju","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"149627","DOI":"10.1155\/2014\/149627","article-title":"Functional roles of protein nitration in acute and chronic liver diseases","volume":"2014","author":"Abdelmegeed","year":"2014","journal-title":"Oxid. Med. Cell Longev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.cotox.2018.10.003","article-title":"Lipid peroxidation derived reactive aldehydes in alcoholic liver disease","volume":"13","author":"Ali","year":"2019","journal-title":"Curr. Opin. Toxicol."},{"key":"B3","doi-asserted-by":"publisher","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 Radic. Biol. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"23","DOI":"10.4137\/JEN.S39887","article-title":"Reactive oxygen species: physiological and physiopathological effects on synaptic plasticity","volume":"10","author":"Beckhauser","year":"2016","journal-title":"J. Exp. Neurosci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1152\/physrev.00044.2005","article-title":"The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology","volume":"87","author":"Bedard","year":"2007","journal-title":"Physiol. Rev."},{"key":"B6","doi-asserted-by":"crossref","first-page":"163","DOI":"10.35946\/arcr.v38.2.02","article-title":"Alcohol and gut-derived inflammation","volume":"38","author":"Bishehsari","year":"2017","journal-title":"Alcohol Res."},{"key":"B7","first-page":"76","article-title":"Alcohol's role in gastrointestinal tract disorders","volume":"21","author":"Bode","year":"1997","journal-title":"Alcohol Health Res. World"},{"key":"B8","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.jhep.2017.11.006","article-title":"The bidirectional impacts of alcohol consumption and the metabolic syndrome: cofactors for progressive fatty liver disease","volume":"68","author":"Boyle","year":"2018","journal-title":"J. Hepatol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1215333","DOI":"10.3389\/fimmu.2023.1215333","article-title":"NLRP3: a new therapeutic target in alcoholic liver disease","volume":"14","author":"Brahadeeswaran","year":"2023","journal-title":"Front. Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.3390\/nu15071571","article-title":"The influence of alcohol consumption on intestinal nutrient absorption: a comprehensive review","volume":"15","author":"Butts","year":"2023","journal-title":"Nutrients"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2993","DOI":"10.3390\/nu15132993","article-title":"The effect of very-long-chain n-3 polyunsaturated fatty acids in the central nervous system and their potential benefits for treating alcohol use disorder: reviewing pre-clinical and clinical data","volume":"15","author":"Carvajal","year":"2023","journal-title":"Nutrients"},{"key":"B12","doi-asserted-by":"publisher","first-page":"3626","DOI":"10.3390\/molecules24193626","article-title":"Red wine consumption and cardiovascular health","volume":"24","author":"Castaldo","year":"2019","journal-title":"Molecules"},{"key":"B13","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":"B14","doi-asserted-by":"publisher","first-page":"102753","DOI":"10.1016\/j.ebiom.2020.102753","article-title":"Novel and prevalent non-East Asian ALDH2 variants; Implications for global susceptibility to aldehydes' toxicity","volume":"55","author":"Chen","year":"2020","journal-title":"EBioMedicine"},{"key":"B15","doi-asserted-by":"publisher","first-page":"7421","DOI":"10.3748\/wjg.v12.i46.7421","article-title":"Pathophysiology of alcoholic pancreatitis: an overview","volume":"12","author":"Chowdhury","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"165801","DOI":"10.1016\/j.bbadis.2020.165801","article-title":"Interplay between NADH oxidation by complex I, glutathione redox state and sirtuin-3, and its role in the development of insulin resistance","volume":"1866","author":"Cort\u00e9s-Rojo","year":"2020","journal-title":"Biochimica Biophysica Acta (BBA) - Mol. Basis Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"04","DOI":"10.35946\/arcr.v44.1.04","article-title":"Alcohol, HMGB1, and innate immune signaling in the brain","volume":"44","author":"Crews","year":"2024","journal-title":"Alcohol Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.tips.2017.03.002","article-title":"Titrating tipsy targets: the neurobiology of low-dose alcohol","volume":"38","author":"Cui","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"6949","DOI":"10.3390\/ijms22136949","article-title":"Mitochondrial lipid homeostasis at the crossroads of liver and heart diseases","volume":"22","author":"Dabravolski","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1111\/j.1530-0277.1998.tb03695.x","article-title":"Effects of moderate alcohol consumption on the central nervous system","volume":"22","author":"Eckardt","year":"1998","journal-title":"Alcohol Clin. Exp. Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-981-13-6260-6_1","article-title":"Role of alcohol oxidative metabolism in its cardiovascular and autonomic effects","volume":"1193","author":"EL-Mas","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"e107421","DOI":"10.1371\/journal.pone.0107421","article-title":"Ethanol impairs intestinal barrier function in humans through mitogen activated protein kinase signaling: a combined in vivo and in vitro approach","volume":"9","author":"Elamin","year":"2014","journal-title":"PLoS One"},{"key":"B23","doi-asserted-by":"publisher","first-page":"100220","DOI":"10.1016\/j.jhepr.2020.100220","article-title":"Gut dysbiosis as a driver in alcohol-induced liver injury","volume":"3","author":"Fairfield","year":"2021","journal-title":"JHEP Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1097\/HEP.0000000000000890","article-title":"Alcohol-associated liver cancer","volume":"80","author":"Fu","year":"2024","journal-title":"Hepatology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.3969\/j.issn.1673-5374.2013.21.009","article-title":"Oxidative stress, mitochondrial damage and neurodegenerative diseases","volume":"8","author":"Guo","year":"2013","journal-title":"Neural Regen. Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"106218","DOI":"10.1016\/j.jff.2024.106218","article-title":"Anti-inflammatory effects of ginsenoside compound K in ethanol-stimulated macrophages by modulating sirtuin 1","volume":"117","author":"Gwon","year":"2024","journal-title":"J. Funct. Foods"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1017\/S000711451500077X","article-title":"Adipose tissue hypoxia and low-grade inflammation: a possible mechanism for ethanol-related glucose intolerance?","volume":"113","author":"He","year":"2015","journal-title":"Br. J. Nutr."},{"key":"B28","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1007\/s11906-011-0194-y","article-title":"Alcohol consumption, blood pressure, and the risk of stroke","volume":"13","author":"Hillbom","year":"2011","journal-title":"Curr. Hypertens. Rep."},{"key":"B29","doi-asserted-by":"publisher","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":"B30","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1002\/hep.24708","article-title":"Regulation of hepatic lipin-1 by ethanol: role of AMP-activated protein kinase\/sterol regulatory element-binding protein 1 signaling in mice","volume":"55","author":"Hu","year":"2012","journal-title":"Hepatology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/S0929-6646(09)60374-0","article-title":"Alterations in oxidative stress status during early alcohol withdrawal in alcoholic patients","volume":"108","author":"Huang","year":"2009","journal-title":"J. Formos. Med. Assoc."},{"key":"B32","doi-asserted-by":"publisher","first-page":"245","DOI":"10.4330\/wjc.v6.i5.245","article-title":"Alcohol-induced hypertension: mechanism and prevention","volume":"6","author":"Husain","year":"2014","journal-title":"World J. Cardiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1111\/j.1365-2265.1995.tb02033.x","article-title":"The effects of alcoholism on the hypothalamic-pituitary-adrenal axis: interaction with endogenous opioid peptides","volume":"43","author":"Inder","year":"1995","journal-title":"Clin. Endocrinol. (Oxf)"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.3389\/fphar.2020.01225","article-title":"SIRT1 activation by natural phytochemicals: an overview","volume":"11","author":"Iside","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"951","DOI":"10.5114\/aoms.2014.46215","article-title":"The alcohol dehydrogenase isoenzyme alcohol dehydrogenase IV as a candidate marker of Helicobacter pylori infection","volume":"10","author":"Jelski","year":"2014","journal-title":"Arch. Med. Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1194\/jlr.R119000547","article-title":"Alcohol effects on hepatic lipid metabolism","volume":"61","author":"Jeon","year":"2020","journal-title":"J. Lipid Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"50","DOI":"10.3390\/biomedicines8030050","article-title":"Alcohol metabolizing enzymes, microsomal ethanol oxidizing system, cytochrome P450 2E1, catalase, and aldehyde dehydrogenase in alcohol-associated liver disease","volume":"8","author":"Jiang","year":"2020","journal-title":"Biomedicines"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e554","DOI":"10.1038\/cddis.2013.78","article-title":"Regulation of cytochrome P450 2e1 expression by ethanol: role of oxidative stress-mediated pkc\/jnk\/sp1 pathway","volume":"4","author":"Jin","year":"2013","journal-title":"Cell Death & Dis."},{"key":"B39","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1111\/j.1530-0277.2010.01420.x","article-title":"The change of plasma ghrelin and leptin levels by the development of type 2 diabetes mellitus in patients with alcohol dependence","volume":"35","author":"Ju","year":"2011","journal-title":"Alcohol Clin. Exp. Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"4642","DOI":"10.3390\/ijms22094642","article-title":"The Chemistry of reactive oxygen species (ROS) Revisited: Outlining their role in Biological Macromolecules (DNA, lipids and proteins) and induced pathologies","volume":"22","author":"Juan","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"108477","DOI":"10.1016\/j.jnutbio.2020.108477","article-title":"Astaxanthin inhibits alcohol-induced inflammation and oxidative stress in macrophages in a sirtuin 1-dependent manner","volume":"85","author":"Kang","year":"2020","journal-title":"J. Nutr. Biochem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"158838","DOI":"10.1016\/j.bbalip.2020.158838","article-title":"Inhibition of alcohol-induced inflammation and oxidative stress by astaxanthin is mediated by its opposite actions in the regulation of sirtuin 1 and histone deacetylase 4 in macrophages","volume":"1866","author":"Kang","year":"","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1038\/s41374-021-00599-1","article-title":"Nicotinamide riboside, an NAD(+) precursor, attenuates inflammation and oxidative stress by activating sirtuin 1 in alcohol-stimulated macrophages","volume":"101","author":"Kang","year":"","journal-title":"Lab. Invest"},{"key":"B44","doi-asserted-by":"publisher","first-page":"108852","DOI":"10.1016\/j.jnutbio.2021.108852","article-title":"A mouse model of the regression of alcoholic hepatitis: Monitoring the regression of hepatic steatosis, inflammation, oxidative stress, and NAD(+) metabolism upon alcohol withdrawal","volume":"99","author":"Kang","year":"2022","journal-title":"J. Nutr. Biochem."},{"key":"B45","doi-asserted-by":"publisher","first-page":"3328","DOI":"10.3390\/ijms20133328","article-title":"The NLRP3 inflammasome: an overview of mechanisms of activation and regulation","volume":"20","author":"Kelley","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"108","DOI":"10.4093\/dmj.2012.36.2.108","article-title":"Alcoholism and diabetes mellitus","volume":"36","author":"Kim","year":"2012","journal-title":"Diabetes Metab. J."},{"key":"B47","doi-asserted-by":"publisher","first-page":"37251","DOI":"10.1074\/jbc.M110.142315","article-title":"Chronic ethanol consumption-induced pancreatic {beta}-cell dysfunction and apoptosis through glucokinase nitration and its down-regulation","volume":"285","author":"Kim","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B48","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.appet.2008.03.011","article-title":"Is decreased appetite for food a physiological consequence of alcohol consumption?","volume":"51","author":"Kokavec","year":"2008","journal-title":"Appetite"},{"key":"B49","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1146\/annurev-pharmtox-031323-115847","article-title":"Alcohol use disorder treatment: problems and solutions","volume":"64","author":"Koob","year":"2024","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"B50","first-page":"274","article-title":"Alcohol metabolism's damaging effects on the cell: a focus on reactive oxygen generation by the enzyme cytochrome P450 2E1","volume":"29","author":"Koop","year":"2006","journal-title":"Alcohol Res. Health"},{"key":"B51","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.yjmcc.2011.10.011","article-title":"Moderate ethanol ingestion and cardiovascular protection: from epidemiologic associations to cellular mechanisms","volume":"52","author":"Krenz","year":"2012","journal-title":"J. Mol. Cell Cardiol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2101","DOI":"10.3390\/ijms22042101","article-title":"Lycopene inhibits oxidative stress-mediated inflammatory responses in ethanol\/Palmitoleic acid-stimulated pancreatic Acinar AR42J cells","volume":"22","author":"Lee","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1002\/path.6372","article-title":"Nicotinamide riboside targets mitochondrial unfolded protein response to reduce alcohol-induced damage in Kupffer cells","volume":"265","author":"Lee","year":"2025","journal-title":"J. Pathol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"778456","DOI":"10.3389\/fnbeh.2021.778456","article-title":"Alcohol-induced neuroinflammatory response and mitochondrial dysfunction on aging and Alzheimer's disease","volume":"15","author":"Le\u00f3n","year":"2021","journal-title":"Front. Behav. Neurosci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3390\/biom13010002","article-title":"Alcohol, resistance Exercise, and mTOR pathway signaling: an evidence-Based Narrative review","volume":"13","author":"Levitt","year":"2022","journal-title":"Biomolecules"},{"key":"B56","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.livres.2017.03.004","article-title":"Adipose tissue autophagy and homeostasis in alcohol-induced liver injury","volume":"1","author":"Li","year":"2017","journal-title":"Liver Res."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1677\/joe-09-0260","article-title":"Current views on type 2 diabetes","volume":"204","author":"Lin","year":"2010","journal-title":"J. Endocrinol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1080\/00952990.2019.1669629","article-title":"Changes in the composition of the human intestinal microbiome in alcohol use disorder: a systematic review","volume":"46","author":"Litwinowicz","year":"2020","journal-title":"Am. J. Drug Alcohol Abuse"},{"key":"B59","doi-asserted-by":"publisher","first-page":"111212","DOI":"10.1016\/j.mad.2020.111212","article-title":"Mitochondrial fission and fusion: a dynamic role in aging and potential target for age-related disease","volume":"186","author":"Liu","year":"2020","journal-title":"Mech. Ageing Dev."},{"key":"B60","doi-asserted-by":"publisher","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 Radic. Biol. Med."},{"key":"B61","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.jtbi.2008.05.033","article-title":"Role of the malate-aspartate shuttle on the metabolic response to myocardial ischemia","volume":"254","author":"Lu","year":"2008","journal-title":"J. Theor. Biol."},{"key":"B62","first-page":"134","article-title":"The role of thiamine deficiency in alcoholic brain disease","volume":"27","author":"Martin","year":"2003","journal-title":"Alcohol Res. Health"},{"key":"B63","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.rec.2024.01.006","article-title":"Effect of the Mediterranean diet in cardiovascular prevention","volume":"77","author":"Mart\u00ednez-Gonz\u00e1lez","year":"2024","journal-title":"Rev. Esp. Cardiol. Engl. Ed."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1002\/hep.32675","article-title":"Adipose lipolysis is important for ethanol to induce fatty liver in the National Institute on Alcohol Abuse and Alcoholism murine model of chronic and binge ethanol feeding","volume":"77","author":"Mathur","year":"2023","journal-title":"Hepatology"},{"key":"B65","first-page":"433","article-title":"Understanding the pathogenesis and treatment of insulin resistance and type 2 diabetes mellitus: what can we learn from transgenic and knockout mice?","volume":"26","author":"Mauvais-Jarvis","year":"2000","journal-title":"Diabetes Metab."},{"key":"B66","doi-asserted-by":"publisher","first-page":"170","DOI":"10.3390\/biom8040170","article-title":"Role of HIF-1\u03b1 in alcohol-mediated multiple organ dysfunction","volume":"8","author":"Morris","year":"2018","journal-title":"Biomolecules"},{"key":"B67","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1002\/hep.24256","article-title":"Hepatocyte-specific hypoxia-inducible factor-1\u03b1 is a determinant of lipid accumulation and liver injury in alcohol-induced steatosis in mice","volume":"53","author":"Nath","year":"2011","journal-title":"Hepatology"},{"key":"B68","doi-asserted-by":"publisher","first-page":"3938","DOI":"10.3390\/nu13113938","article-title":"Alcohol and the brain","volume":"13","author":"Nutt","year":"2021","journal-title":"Nutrients"},{"key":"B69","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.pcad.2018.02.001","article-title":"Alcohol and CV health: Jekyll and Hyde J-Curves","volume":"61","author":"O'Keefe","year":"2018","journal-title":"Prog. Cardiovasc Dis."},{"key":"B70","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.fob.2015.06.001","article-title":"Reactive oxygen species induce Cox-2 expression via TAK1 activation in synovial fibroblast cells","volume":"5","author":"Onodera","year":"2015","journal-title":"FEBS Open Bio"},{"key":"B71","first-page":"125","article-title":"Alcoholism and the brain: an overview","volume":"27","author":"Oscar-Berman","year":"2003","journal-title":"Alcohol Res. Health"},{"key":"B72","doi-asserted-by":"crossref","first-page":"147","DOI":"10.35946\/arcr.v38.2.01","article-title":"Alcoholic liver disease: pathogenesis and current Management","volume":"38","author":"Osna","year":"2017","journal-title":"Alcohol Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1111\/acer.14299","article-title":"Perturbations in mitochondrial dynamics are closely involved in the progression of alcoholic liver disease","volume":"44","author":"Palma","year":"2020","journal-title":"Alcohol Clin. Exp. Res."},{"key":"B74","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.jcmgh.2022.10.002","article-title":"Ethanol and its Nonoxidative metabolites promote acute liver injury by inducing ER stress, Adipocyte death, and lipolysis","volume":"15","author":"Park","year":"2023","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"2573","DOI":"10.3390\/biom5042573","article-title":"Alcohol and the intestine","volume":"5","author":"Patel","year":"2015","journal-title":"Biomolecules"},{"key":"B76","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/j.bbamcr.2012.02.019","article-title":"Signaling the mitochondrial unfolded protein response","volume":"1833","author":"Pellegrino","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"B77","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.numecd.2009.05.014","article-title":"Alcohol consumption and cardiovascular risk factors in older lifelong wine drinkers: the Italian Longitudinal Study on Aging","volume":"20","author":"Perissinotto","year":"2010","journal-title":"Nutr. Metab. Cardiovasc Dis."},{"key":"B78","doi-asserted-by":"publisher","first-page":"390","DOI":"10.3934\/Neuroscience.2021021","article-title":"Effect of alcohol on the central nervous system to develop neurological disorder: pathophysiological and lifestyle modulation can be potential therapeutic options for alcohol-induced neurotoxication","volume":"8","author":"Pervin","year":"2021","journal-title":"AIMS Neurosci."},{"key":"B79","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.physbeh.2008.01.020","article-title":"Type 2 diabetes mellitus and skeletal muscle metabolic function","volume":"94","author":"Phielix","year":"2008","journal-title":"Physiol. Behav."},{"key":"B80","doi-asserted-by":"publisher","first-page":"S155","DOI":"10.1007\/s40279-014-0255-x","article-title":"Can antioxidants protect against disuse muscle atrophy?","volume":"44","author":"Powers","year":"2014","journal-title":"Sports Med."},{"key":"B81","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1016\/s0891-5849(01)00794-8","article-title":"Free radicals in alcoholic myopathy: indices of damage and preventive studies","volume":"32","author":"Preedy","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"B82","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1007\/s40265-023-01939-9","article-title":"Alcohol-associated liver disease: Evolving Concepts and treatments","volume":"83","author":"Prince","year":"2023","journal-title":"Drugs"},{"key":"B83","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.alcohol.2017.01.011","article-title":"Quantifying the contribution of alcohol to cardiomyopathy: a systematic review","volume":"61","author":"Rehm","year":"2017","journal-title":"Alcohol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1016\/s1542-3565(05)00743-3","article-title":"Joint effects of body weight and alcohol on elevated serum alanine aminotransferase in the United States population","volume":"3","author":"Ruhl","year":"2005","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"627","DOI":"10.3390\/antiox14060627","article-title":"Lactobacillus rhamnosus GG modulates mitochondrial function and antioxidant responses in an ethanol-exposed in vivo model: evidence of HIGD2A-dependent OXPHOS remodeling in the liver","volume":"14","author":"Salazar","year":"2025","journal-title":"Antioxidants (Basel)"},{"key":"B86","doi-asserted-by":"publisher","first-page":"5537","DOI":"10.3390\/molecules26185537","article-title":"Wine, polyphenols, and Mediterranean diets. What else is there to say?","volume":"26","author":"Santos-Buelga","year":"2021","journal-title":"Molecules"},{"key":"B87","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1093\/alcalc\/agx013","article-title":"Long-term mortality of patients with an alcohol-related Wernicke\u2013korsakoff syndrome","volume":"52","author":"Sanvisens","year":"2017","journal-title":"Alcohol Alcohol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.ceb.2015.02.003","article-title":"Acetyl-CoA and the regulation of metabolism: mechanisms and consequences","volume":"33","author":"Shi","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1038\/s41598-020-80637-y","article-title":"Chronic stress and corticosterone exacerbate alcohol-induced tissue injury in the gut-liver-brain axis","volume":"11","author":"Shukla","year":"2021","journal-title":"Sci. Rep."},{"key":"B90","doi-asserted-by":"publisher","first-page":"8650","DOI":"10.3390\/ijms24108650","article-title":"Mitochondrial dysfunction: at the nexus between alcohol-associated immunometabolic dysregulation and tissue injury","volume":"24","author":"Siggins","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B91","doi-asserted-by":"crossref","first-page":"207","DOI":"10.35946\/arcr.v38.2.05","article-title":"Alcoholic myopathy: pathophysiologic mechanisms and clinical Implications","volume":"38","author":"Simon","year":"2017","journal-title":"Alcohol Res."},{"key":"B92","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1007\/s10753-020-01242-9","article-title":"Role of Silent Information regulator 1 (SIRT1) in regulating oxidative stress and inflammation","volume":"43","author":"Singh","year":"2020","journal-title":"Inflammation"},{"key":"B93","doi-asserted-by":"publisher","first-page":"E699","DOI":"10.1152\/ajpendo.00006.2015","article-title":"Dysregulation of skeletal muscle protein metabolism by alcohol","volume":"308","author":"Steiner","year":"2015","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B94","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3390\/biom7010016","article-title":"Alcohol, adipose tissue and lipid dysregulation","volume":"7","author":"Steiner","year":"2017","journal-title":"Biomolecules"},{"key":"B95","doi-asserted-by":"publisher","first-page":"2223","DOI":"10.3390\/biom5042223","article-title":"Impact of alcohol on Glycemic control and insulin action","volume":"5","author":"Steiner","year":"2015","journal-title":"Biomolecules"},{"key":"B96","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1053\/he.2000.5634","article-title":"Kupffer cell activation by lipopolysaccharide in rats: role for lipopolysaccharide binding protein and toll-like receptor 4","volume":"31","author":"Su","year":"2000","journal-title":"Hepatology"},{"key":"B97","doi-asserted-by":"publisher","first-page":"463.e1","DOI":"10.1016\/j.ajog.2014.01.045","article-title":"In utero exposure to a maternal high-fat diet alters the epigenetic histone code in a murine model","volume":"210","author":"Suter","year":"2014","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B98","doi-asserted-by":"publisher","first-page":"220S","DOI":"10.1097\/01.alc.0000190657.97988.c7","article-title":"Cytotoxicity of acetaldehyde-derived advanced glycation end-products (AA-AGE) in alcoholic-induced neuronal degeneration","volume":"29","author":"Takeuchi","year":"2005","journal-title":"Alcohol Clin. Exp. Res."},{"key":"B99","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.3390\/antiox11071374","article-title":"Alcohol-induced oxidative stress and the role of antioxidants in alcohol Use disorder: a systematic review","volume":"11","author":"Tsermpini","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"B100","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.bbi.2024.04.022","article-title":"PCSK9 inhibition attenuates alcohol-associated neuronal oxidative stress and cellular injury","volume":"119","author":"Wagner","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"B101","first-page":"300","article-title":"Endotoxin and Kupffer cell activation in alcoholic liver disease","volume":"27","author":"Wheeler","year":"2003","journal-title":"Alcohol Res. Health"},{"key":"B102","doi-asserted-by":"publisher","first-page":"109638","DOI":"10.1016\/j.mehy.2020.109638","article-title":"Ethanol metabolism: the good, the bad, and the ugly","volume":"140","author":"Wilson","year":"2020","journal-title":"Med. Hypotheses"},{"key":"B103","volume-title":"Global status report on alcohol and health and treatment of substance use disorders","year":"2024"},{"key":"B104","first-page":"277","article-title":"Alcohol, oxidative stress, and free radical damage","volume":"27","author":"Wu","year":"2003","journal-title":"Alcohol Res. Health"},{"key":"B105","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/s41392-020-00311-7","article-title":"NAD(+) metabolism: pathophysiologic mechanisms and therapeutic potential","volume":"5","author":"Xie","year":"2020","journal-title":"Signal Transduct. Target Ther."},{"key":"B106","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1172\/JCI17797","article-title":"The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice","volume":"112","author":"Xu","year":"2003","journal-title":"J. Clin. Invest"},{"key":"B107","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1186\/s12967-023-04166-8","article-title":"Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease","volume":"21","author":"Yan","year":"2023","journal-title":"J. Transl. Med."},{"key":"B108","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1111\/acer.12069","article-title":"Alcohol dehydrogenase-1B genotype (rs1229984) is a strong determinant of the relationship between body weight and alcohol intake in Japanese alcoholic men","volume":"37","author":"Yokoyama","year":"2013","journal-title":"Alcohol Clin. Exp. Res."},{"key":"B109","first-page":"245","article-title":"Overview: how is alcohol metabolized by the body?","volume":"29","author":"Zakhari","year":"2006","journal-title":"Alcohol Res. Health"},{"key":"B110","doi-asserted-by":"publisher","first-page":"20408","DOI":"10.1074\/jbc.M109.016469","article-title":"Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene Promoters","volume":"284","author":"Zhang","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B111","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1002\/hep.30945","article-title":"Paneth cell dysfunction Mediates alcohol-related steatohepatitis through promoting bacterial translocation in mice: role of Zinc deficiency","volume":"71","author":"Zhong","year":"2020","journal-title":"Hepatology"}],"container-title":["Frontiers in Toxicology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2025.1670769\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T05:27:16Z","timestamp":1759123636000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/ftox.2025.1670769\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,29]]},"references-count":111,"alternative-id":["10.3389\/ftox.2025.1670769"],"URL":"https:\/\/doi.org\/10.3389\/ftox.2025.1670769","relation":{},"ISSN":["2673-3080"],"issn-type":[{"value":"2673-3080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,29]]},"article-number":"1670769"}}