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ALD is one of the major causes of global burden, yet there are no FDA\u2010approved treatment options available. This study evaluates the hepatoprotective effects of short\u2010chain fatty acids (SCFAs), mainly sodium acetate (NaA) and sodium butyrate (NaB), against ethanol\u2010induced inflammation and oxidative stress in both in vitro (Buffalo Rat Liver\u20103A [BRL3A]) and in vivo (male Wistar rats) models. The treatment of NaA and NaB and their combination was given to the cell lines where maximum viability was observed at concentrations of 1.5\u2009mM, 5\u2009mM, and 0.1 mM\u2009+\u20091 mM, respectively. Additionally, reactive oxygen species (ROS) and nuclear morphology were assessed by fluorescent staining. For in vivo samples, the hepatic injury was analyzed by serum biochemical markers. Furthermore, hematoxylin and eosin (H&amp;E) staining and immunohistochemistry (IHC) staining were employed, which provided structural and immunological alterations in hepatic tissue. RT\u2010qPCR profiled the expression levels of various pro\u2010inflammatory and anti\u2010inflammatory cytokines, as well as cytochrome P450 E1 (CYP2E1) and antioxidative stress markers. Moreover, enzyme\u2010linked immunosorbent assay (ELISA) quantified the essential protein targets such as TNF\u2010\u03b1, MCP\u20101, IL\u20101\u03b2, IL\u20106, HO\u20101, and Nrf2. The administration of NaA, NaB, and their combination resulted in reduced ROS levels and expression of pro\u2010inflammatory cytokines, preserved nuclear integrity, and neutrophil infiltration. These findings were further confirmed by in silico analysis and conserved amino acid interactions, and the affinities of NaA and NaB for TNF\u2010\u03b1 and MCP\u20101 were observed as compared to established inhibitors or activators. This study is the first demonstration to report the synergistic effects of NaA and NaB on the feedback loop of the nuclear factor kappa B (NF\u2010\u03baB) signaling pathway, suggesting their potential as promising therapeutic candidates for alleviating alcohol\u2010induced hepatic damage.<\/jats:p>","DOI":"10.1155\/mi\/5835567","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T09:29:28Z","timestamp":1781947768000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic Effect of Sodium Acetate and Sodium Butyrate in Ameliorating Ethanol\u2010Induced Hepatic Inflammation Through Modulation of the NF\u2010\u03baB Signaling Pathway"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3482-4645","authenticated-orcid":false,"given":"Manali","family":"Patel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3917-9663","authenticated-orcid":false,"given":"Hiral","family":"Aghara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashsti","family":"Chadha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6616-8673","authenticated-orcid":false,"given":"Harshrajsinh","family":"Solanki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1072-1018","authenticated-orcid":false,"given":"Dhrubjyoti","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1044-7626","authenticated-orcid":false,"given":"Vijay","family":"Thiruvenkatam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6612-3773","authenticated-orcid":false,"given":"Palash","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,20]]},"reference":[{"key":"e_1_2_11_1_2","first-page":"872","article-title":"Gut Microbiota as a Therapeutic Target in Alcoholic Liver Disease: A Narrative Review","volume":"15","author":"Bhusan Sutar S.","year":"2025","journal-title":"European Journal of Cardiovascular Medicine"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.aohep.2024.101499"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1205821"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119328"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21217894"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells13060485"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21249407"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.03.007"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-025-01291-w"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/sigtrans.2017.23"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00312-6"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000019009.73586.7F"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0225531"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.913842"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/4230599"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1155\/mi\/6733477"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5245197"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.703218"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/metabo13070859"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2025.1539972"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1186892"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.03.030"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.1036042"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2012.07955.x"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu3100858"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2025.117821"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-007-9106-z"},{"key":"e_1_2_11_28_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1074286"},{"key":"e_1_2_11_29_2","doi-asserted-by":"crossref","unstructured":"Ruiz-UribeN. 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