{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:56:01Z","timestamp":1792788961114,"version":"4.5.0"},"reference-count":156,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH-NIAAA","award":["R01AA030793"],"award-info":[{"award-number":["R01AA030793"]}]},{"name":"NIH-NIAAA","award":["P50AA030407-5130"],"award-info":[{"award-number":["P50AA030407-5130"]}]},{"name":"NIH-NIAAA","award":["I01CX002084"],"award-info":[{"award-number":["I01CX002084"]}]},{"name":"Alcohol Center of Research-Nebraska","award":["R01AA030793"],"award-info":[{"award-number":["R01AA030793"]}]},{"name":"Alcohol Center of Research-Nebraska","award":["P50AA030407-5130"],"award-info":[{"award-number":["P50AA030407-5130"]}]},{"name":"Alcohol Center of Research-Nebraska","award":["I01CX002084"],"award-info":[{"award-number":["I01CX002084"]}]},{"name":"Department of Veterans Affairs","award":["R01AA030793"],"award-info":[{"award-number":["R01AA030793"]}]},{"name":"Department of Veterans Affairs","award":["P50AA030407-5130"],"award-info":[{"award-number":["P50AA030407-5130"]}]},{"name":"Department of Veterans Affairs","award":["I01CX002084"],"award-info":[{"award-number":["I01CX002084"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Alcohol-associated liver disease (ALD) is a major health problem of global importance, caused by chronic alcohol consumption, leading to the accumulation of reactive oxygen species (ROS) and subsequent oxidative stress\u2014a central mechanism in liver injury. Superoxide dismutase 1 (SOD1), a Cu-Zn containing antioxidant enzyme, plays a crucial role in attenuating ALD-induced oxidative stress triggered by ethanol metabolism. However, alcohol exposure, whether chronic, acute or binge, differentially affects SOD1 levels, either diminishing its expression or temporarily compensating for alcohol-induced oxidative damage. Regardless, overexpression of SOD1 reverses early stages of ethanol-induced liver inflammation and injury in animal models, highlighting the protective role of SOD1. Current therapies, including alcohol abstinence, corticosteroids, and pentoxifylline, have limited long-term efficacy. Antioxidant-based treatments, such as N-acetylcysteine (NAC) and S-adenosyl-L-methionine (SAM), have demonstrated moderate benefits. While combination therapies like NAC with prednisolone yield more promising outcomes, these benefits are often limited in duration. The use of natural compounds including nutraceuticals and probiotics provide liver protection by enhancing antioxidant defenses, reducing inflammation, and mitigating alcohol-induced liver damage. In particular, these compounds upregulate antioxidant enzymes like SOD1. Recent research suggests that enhancing the activity of SOD1, particularly through nanoformulated SOD1 (NanoSOD1), which had direct effect on the oxidative stress at the cellular level, could offer a promising therapeutic option for ALD. NanoSOD1 aims to improve the bioavailability and stability of SOD1, offering a targeted approach to reduce oxidative stress and protect against liver damage. The effectiveness of NanoSOD1 to improve antioxidant defenses suggests a valuable therapeutic arsenal in ALD treatment. Taken together, given the limited treatment options for ALD, increasing SOD1 activity is essential for managing the progression of the disease.<\/jats:p>","DOI":"10.3390\/biology14101319","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T07:46:49Z","timestamp":1758786409000},"page":"1319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Pathophysiology of Alcohol-Associated Liver Disease: Focusing on Superoxide Dismutase 1 as a Therapeutic Target"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1031-6300","authenticated-orcid":false,"given":"Thiyagarajan","family":"Gopal","sequence":"first","affiliation":[{"name":"Centre for Laboratory Animal Technology and Research, Sathyabama Institute of Science and Technology, Chennai 600119, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5555-3380","authenticated-orcid":false,"given":"Arul Daniel","family":"John Kathiravan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"VA Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander V.","family":"Kabanov","sequence":"additional","affiliation":[{"name":"Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7501-0495","authenticated-orcid":false,"given":"Carol A.","family":"Casey","sequence":"additional","affiliation":[{"name":"VA Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA"},{"name":"Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viswanathan","family":"Saraswathi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"VA Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41575-022-00688-6","article-title":"Global epidemiology of alcohol-associated cirrhosis and HCC: Trends, projections and risk factors","volume":"20","author":"Huang","year":"2023","journal-title":"Nat. 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