{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:17:02Z","timestamp":1792801022324,"version":"4.5.0"},"reference-count":129,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,6,9]],"date-time":"2024-06-09T00:00:00Z","timestamp":1717891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    This review delves into the detrimental impact of alcohol consumption on internal organs and reproductive health, elucidating the underlying mechanisms involving the\n                    <jats:italic>Toll\u2010like receptor 4 (TLR4)<\/jats:italic>\n                    \/Nuclear factor kappa light chain enhancer of activated B cells (NF\u2010kB) pathway and the Cytochrome P450 2E1 (CYP2E1)\/reactive oxygen species (ROS)\/nuclear factor erythroid 2\u2010related factor 2 (Nrf2) pathways. The\n                    <jats:italic>TLR4\/NF\u2010kB<\/jats:italic>\n                    pathway, crucial for inflammatory and immune responses, triggers the production of pro\u2010inflammatory agents and type\u20101 interferon, disrupting the balance between inflammatory and antioxidant responses when tissues are chronically exposed to alcohol. Alcohol\u2010induced dysbiosis in gut microbes heightens gut wall permeability to pathogen\u2010associated molecular patterns (PAMPs), leading to liver cell infection and subsequent inflammation. Concurrently, CYP2E1\u2010mediated alcohol metabolism generates ROS, causing oxidative stress and damaging cells, lipids, proteins, and deoxyribonucleic acid (DNA). To counteract this inflammatory imbalance, Nrf2 regulates gene expression, inhibiting inflammatory progression and promoting antioxidant responses. Excessive alcohol intake results in elevated liver enzymes (ADH, CYP2E1, and catalase), ROS, NADH, acetaldehyde, and acetate, leading to damage in vital organs such as the heart, brain, and lungs. Moreover, alcohol negatively affects reproductive health by inhibiting the hypothalamic\u2013pituitary\u2010gonadal axis, causing infertility in both men and women. These findings underscore the profound health concerns associated with alcohol\u2010induced damage, emphasizing the need for public awareness regarding the intricate interplay between immune responses and the multi\u2010organ impacts of alcohol consumption.\n                  <\/jats:p>","DOI":"10.1002\/ame2.12436","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:18:56Z","timestamp":1717978736000},"page":"444-459","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Uncovering the impact of alcohol on internal organs and reproductive health: Exploring\n                    <i>TLR4\/NF\u2010kB<\/i>\n                    and CYP2E1\/ROS\/Nrf2 pathways"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8128-1955","authenticated-orcid":false,"given":"Eason Qi Zheng","family":"Kong","sequence":"first","affiliation":[{"name":"Pharmacology Unit, Jeffrey Cheah School of Medicine and Health Sciences Monash University Malaysia  Subang Jaya Selangor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vetriselvan","family":"Subramaniyan","sequence":"additional","affiliation":[{"name":"Pharmacology Unit, Jeffrey Cheah School of Medicine and Health Sciences Monash University Malaysia  Subang Jaya Selangor Malaysia"},{"name":"Center for Global Health Research, Saveetha Medical College Saveetha Institute of Medical and Technical Sciences  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha Sura Anak","family":"Lubau","sequence":"additional","affiliation":[{"name":"Pharmacology Unit, Jeffrey Cheah School of Medicine and Health Sciences Monash University Malaysia  Subang Jaya Selangor Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,9]]},"reference":[{"issue":"7","key":"e_1_2_18_2_1","article-title":"The impact of oxidative stress on male reproductive function: exploring the role of antioxidant supplementation","volume":"15","author":"Walke G","year":"2023","journal-title":"Cureus"},{"key":"e_1_2_18_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-060821-014008"},{"key":"e_1_2_18_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2023.10.005"},{"key":"e_1_2_18_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6866"},{"key":"e_1_2_18_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03337-3"},{"key":"e_1_2_18_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-021-10033-4"},{"key":"e_1_2_18_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25225474"},{"key":"e_1_2_18_9_1","doi-asserted-by":"publisher","DOI":"10.29252\/nfsr.7.2.13"},{"key":"e_1_2_18_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph19010328"},{"key":"e_1_2_18_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8111981"},{"key":"e_1_2_18_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2021.02.010"},{"key":"e_1_2_18_13_1","first-page":"211","volume-title":"Stem Cells and Cancer in Hepatology","author":"Naoto K","year":"2018"},{"key":"e_1_2_18_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines5040034"},{"key":"e_1_2_18_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-409547-2.12400-X"},{"key":"e_1_2_18_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-804019-5.00006-2"},{"key":"e_1_2_18_17_1","first-page":"293","volume-title":"Systemic Lupus Erythematosus","author":"Terry KM","year":"2011"},{"key":"e_1_2_18_18_1","first-page":"281","volume-title":"Nutrition in the Prevention and Treatment of Abdominal Obesity","author":"Yoshinori N","year":"2014"},{"key":"e_1_2_18_19_1","first-page":"37","volume-title":"Annual Reports in Medicinal Chemistry","author":"Allen TH","year":"2012"},{"key":"e_1_2_18_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1104780108"},{"key":"e_1_2_18_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1222811110"},{"key":"e_1_2_18_22_1","first-page":"45","volume-title":"Vaccines for Cancer Immunotherapy","author":"Mahsa K\u2010F","year":"2019"},{"key":"e_1_2_18_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep13128"},{"key":"e_1_2_18_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09121"},{"key":"e_1_2_18_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034202"},{"key":"e_1_2_18_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3713"},{"key":"e_1_2_18_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.08.006"},{"key":"e_1_2_18_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2009.12.023"},{"key":"e_1_2_18_29_1","first-page":"2039","volume-title":"Mucosal Immunology","author":"Ines A","year":"2015"},{"key":"e_1_2_18_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa2630"},{"key":"e_1_2_18_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3581"},{"key":"e_1_2_18_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3787"},{"key":"e_1_2_18_33_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X18666200207120949"},{"issue":"4","key":"e_1_2_18_34_1","first-page":"453","article-title":"Nuclear factor\u2010\u03baB\u2010importance, induction of inflammation, and effects of pharmacological modulators in Crohn's disease","volume":"71","author":"Szatkowski P","year":"2020","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_18_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-020-03524-9"},{"key":"e_1_2_18_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2013.01.004"},{"key":"e_1_2_18_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.177"},{"key":"e_1_2_18_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-015-0056-4"},{"key":"e_1_2_18_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology12060776"},{"key":"e_1_2_18_40_1","doi-asserted-by":"publisher","DOI":"10.32471\/exp-oncology.2312-8852.vol-42-no-4.15414"},{"key":"e_1_2_18_41_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-19-0087"},{"key":"e_1_2_18_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01088.x"},{"key":"e_1_2_18_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2011.1"},{"key":"e_1_2_18_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2023.111470"},{"issue":"1","key":"e_1_2_18_45_1","first-page":"96","article-title":"Phytochemicals and regulation of NF\u2010kB in inflammatory bowel diseases: an overview of in\u00a0vitro and in\u00a0vivo effects","volume":"13","author":"Laurindo LF","year":"2023","journal-title":"Meta"},{"key":"e_1_2_18_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.78"},{"key":"e_1_2_18_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03396-6"},{"key":"e_1_2_18_48_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/4680732"},{"key":"e_1_2_18_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0225531"},{"key":"e_1_2_18_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e04602"},{"key":"e_1_2_18_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep29423"},{"key":"e_1_2_18_52_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2019.10890"},{"key":"e_1_2_18_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2014.09.004"},{"key":"e_1_2_18_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-015-4269-x"},{"key":"e_1_2_18_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology10050384"},{"key":"e_1_2_18_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2016.09.012"},{"key":"e_1_2_18_57_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-12-1424"},{"key":"e_1_2_18_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-0384-2"},{"key":"e_1_2_18_59_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201102095"},{"key":"e_1_2_18_60_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4350965"},{"key":"e_1_2_18_61_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9912436"},{"key":"e_1_2_18_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15068"},{"key":"e_1_2_18_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2016.11.005"},{"key":"e_1_2_18_64_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.5149"},{"key":"e_1_2_18_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.7407"},{"key":"e_1_2_18_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2024.112389"},{"key":"e_1_2_18_67_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21134777"},{"key":"e_1_2_18_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.05.034"},{"key":"e_1_2_18_69_1","first-page":"43","volume-title":"Current Concepts in Drug Metabolism and Toxicology","author":"Ian MC","year":"2012"},{"key":"e_1_2_18_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-804274-8.00028-X"},{"key":"e_1_2_18_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks827"},{"key":"e_1_2_18_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-08-046884-6.00227-X"},{"key":"e_1_2_18_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2013.07.005"},{"key":"e_1_2_18_74_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21249698"},{"key":"e_1_2_18_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.07.025"},{"key":"e_1_2_18_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2011.04.002"},{"key":"e_1_2_18_77_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.773960"},{"key":"e_1_2_18_78_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst20150014"},{"key":"e_1_2_18_79_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.967193"},{"key":"e_1_2_18_80_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21249407"},{"key":"e_1_2_18_81_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.797123"},{"key":"e_1_2_18_82_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph7031076"},{"key":"e_1_2_18_83_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22115717"},{"key":"e_1_2_18_84_1","first-page":"261","volume-title":"Molecular Aspects of Alcohol and Nutrition","author":"Claudio DA","year":"2016"},{"key":"e_1_2_18_85_1","doi-asserted-by":"publisher","DOI":"10.4161\/oxim.3.3.12288"},{"issue":"4","key":"e_1_2_18_86_1","first-page":"245","article-title":"Overview: how is alcohol metabolized by the body?","volume":"29","author":"Zakhari S","year":"2006","journal-title":"Alcohol Res Health"},{"key":"e_1_2_18_87_1","first-page":"306","volume-title":"Nelson Pediatric Symptom\u2010Based Diagnosis: Common Diseases and their Mimics","author":"Grzegorz WT","year":"2023"},{"key":"e_1_2_18_88_1","first-page":"71","volume-title":"Reviews of Physiology, Biochemistry and Pharmacology","author":"Luangmonkong T","year":"2018"},{"key":"e_1_2_18_89_1","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1673-5374.2013.21.009"},{"key":"e_1_2_18_90_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00026.2013"},{"issue":"4","key":"e_1_2_18_91_1","first-page":"277","article-title":"Alcohol, oxidative stress, and free radical damage","volume":"27","author":"Wu D","year":"2003","journal-title":"Alcohol Res Health"},{"key":"e_1_2_18_92_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10010092"},{"key":"e_1_2_18_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.04.002"},{"key":"e_1_2_18_94_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094642"},{"key":"e_1_2_18_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-08-046884-6.00406-1"},{"key":"e_1_2_18_96_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-5881-0_8"},{"key":"e_1_2_18_97_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-022-01404-8"},{"key":"e_1_2_18_98_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.4401"},{"key":"e_1_2_18_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2020.109638"},{"key":"e_1_2_18_100_1","first-page":"493","volume-title":"Neuroscience of Alcohol","author":"Joana GM","year":"2019"},{"key":"e_1_2_18_101_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.580167"},{"key":"e_1_2_18_102_1","first-page":"169","volume-title":"Complications in Neuroanesthesia","author":"Pirjo HM","year":"2016"},{"key":"e_1_2_18_103_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7216"},{"key":"e_1_2_18_104_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12263-023-00726-1"},{"key":"e_1_2_18_105_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2020.104842"},{"key":"e_1_2_18_106_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1569"},{"key":"e_1_2_18_107_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00414-015-1159-5"},{"key":"e_1_2_18_108_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2013.01.005"},{"key":"e_1_2_18_109_1","doi-asserted-by":"publisher","DOI":"10.1080\/09168451.2014.910102"},{"issue":"2","key":"e_1_2_18_110_1","first-page":"92","article-title":"Overview of current concepts in gastric intestinal metaplasia and gastric cancer","volume":"14","author":"Jencks DS","year":"2018","journal-title":"Gastroenterol Hepatol (N Y)"},{"key":"e_1_2_18_111_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2022.11.002"},{"key":"e_1_2_18_112_1","first-page":"1313","article-title":"Fatty acid ethyl ester synthase inhibition ameliorates ethanol\u2010induced Ca2+\u2212dependent mitochondrial dysfunction and acute pancreatitis","author":"Huang W","year":"2013","journal-title":"Gut"},{"key":"e_1_2_18_113_1","doi-asserted-by":"publisher","DOI":"10.4291\/wjgp.v7.i1.48"},{"key":"e_1_2_18_114_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12589"},{"key":"e_1_2_18_115_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-022-09767-0"},{"key":"e_1_2_18_116_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-015-0620-1"},{"key":"e_1_2_18_117_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3002902"},{"key":"e_1_2_18_118_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa417"},{"key":"e_1_2_18_119_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu4081058"},{"key":"e_1_2_18_120_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2009.12.030"},{"key":"e_1_2_18_121_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40738-017-0037-x"},{"key":"e_1_2_18_122_1","first-page":"65","volume-title":"Management of Infertility","author":"Stella L","year":"2023"},{"key":"e_1_2_18_123_1","doi-asserted-by":"publisher","DOI":"10.4103\/0974-1208.92283"},{"key":"e_1_2_18_124_1","volume-title":"Reference Module in Biomedical Sciences","author":"Sepideh K","year":"2018"},{"key":"e_1_2_18_125_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje-14-1103"},{"key":"e_1_2_18_126_1","doi-asserted-by":"publisher","DOI":"10.1159\/000354208"},{"key":"e_1_2_18_127_1","doi-asserted-by":"publisher","DOI":"10.29252\/ijrm.14.4.231"},{"key":"e_1_2_18_128_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.23138"},{"key":"e_1_2_18_129_1","doi-asserted-by":"publisher","DOI":"10.30773\/pi.2019.02.28"},{"key":"e_1_2_18_130_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2215-0366(19)30213-5"}],"container-title":["Animal Models and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ame2.12436","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:19:59Z","timestamp":1725581999000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ame2.12436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,9]]},"references-count":129,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/ame2.12436"],"URL":"https:\/\/doi.org\/10.1002\/ame2.12436","archive":["Portico"],"relation":{},"ISSN":["2576-2095","2576-2095"],"issn-type":[{"value":"2576-2095","type":"print"},{"value":"2576-2095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,9]]},"assertion":[{"value":"2023-12-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}