{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T05:43:28Z","timestamp":1787982208952,"version":"build-2784847793"},"reference-count":26,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AA025140"],"award-info":[{"award-number":["AA025140"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AA017626"],"award-info":[{"award-number":["AA017626"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>To date, there is no effective treatment for alcoholic liver disease, despite its prevalence world-wide. Because alcohol consumption is associated with oxidative stress-induced liver injury and pro-inflammatory responses, naturally occurring antioxidants and\/or anti-inflammatories may be potential therapeutics. Spermidine is an abundant, ubiquitous polyamine that has been found to display strong antioxidant and anti-inflammatory properties. To further investigate whether spermidine is an effective intervention for alcohol-induced liver disease, we examined its hepatoprotective properties using a two-hit, chronic ethanol and acute lipopolysaccharide (LPS)-induced mouse model of liver injury. We determined that spermidine administration prevented ethanol and LPS-induced increases in liver injury using plasma ALT as a readout. Furthermore, histological analysis of tissue from control and treated animals revealed that the pathology associated with ethanol and LPS treatment was prevented in mice additionally treated with spermidine. As predicted, spermidine also prevented ethanol and LPS-induced oxidative stress by decreasing the levels of both reactive oxygen species (ROS) and lipid peroxidation. We further determined that spermidine treatment prevented the nuclear translocation of nuclear factor \u03baB (NF\u03baB) by blocking the phosphorylation of the inhibitory protein, I\u03baB, thereby preventing expression of pro-inflammatory cytokines. Finally, by measuring expression of known markers of hepatic stellate cell activation and monitoring collagen deposition, we observed that spermidine also prevented alcohol and LPS-induced hepatic fibrosis. Together, our results indicate that spermidine is an antioxidant thereby conferring anti-inflammatory and anti-fibrotic effects associated with alcoholic liver injury.<\/jats:p>","DOI":"10.3390\/molecules26061786","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T12:55:07Z","timestamp":1616417707000},"page":"1786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Spermidine Prevents Ethanol and Lipopolysaccharide-Induced Hepatic Injury in Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Raghabendra","family":"Adhikari","sequence":"first","affiliation":[{"name":"Department of Biology, The Catholic University of America, Washington DC 20064, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9533-1747","authenticated-orcid":false,"given":"Ruchi","family":"Shah","sequence":"additional","affiliation":[{"name":"Lipid Research Laboratory, VA Medical Center, Washington, DC 20422, USA"},{"name":"Department of Biochemistry and Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Reyes-Gordillo","sequence":"additional","affiliation":[{"name":"Lipid Research Laboratory, VA Medical Center, Washington, DC 20422, USA"},{"name":"Department of Biochemistry and Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037, USA"},{"name":"Division of Microbiology, Office of Regulatory Science, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, College Park, MD 20740, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7363-4870","authenticated-orcid":false,"given":"Jaime","family":"Arellanes-Robledo","sequence":"additional","affiliation":[{"name":"Lipid Research Laboratory, VA Medical Center, Washington, DC 20422, USA"},{"name":"Department of Biochemistry and Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037, USA"},{"name":"Laboratory of Hepatic Diseases; Catedras-CONACYT\u2013National Institute of Genomic Medicine (INMEGEN), Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Cheng","sequence":"additional","affiliation":[{"name":"Lipid Research Laboratory, VA Medical Center, Washington, DC 20422, USA"},{"name":"Department of Biochemistry and Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Lipid Research Laboratory, VA Medical Center, Washington, DC 20422, USA"},{"name":"Department of Biochemistry and Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela L.","family":"Tuma","sequence":"additional","affiliation":[{"name":"Department of Biology, The Catholic University of America, Washington DC 20064, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"ref_1","first-page":"285","article-title":"Dangerous byproducts of alcohol breakdown\u2014Focus on adducts","volume":"27","author":"Tuma","year":"2003","journal-title":"Alcohol. 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