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In ALD, ROS arise from alcohol metabolism (CYP2E1 and ADH\/ALDH2), causing oxidative damage and fibrosis. In NAFLD, mitochondrial dysfunction, ER stress, and lipotoxicity drive ROS overproduction due to metabolic dysregulation. Both diseases share ROS-mediated pathways, including mitochondrial\/ER dysfunction, inflammation, and impaired lipid metabolism, accelerating steatosis to cirrhosis and cancer. Antioxidants, ER modulators, and lifestyle changes show therapeutic potential but require further clinical validation. Future research should leverage multi-omics and targeted therapies to optimize ROS-focused interventions for ALD and NAFLD.<\/jats:p>","DOI":"10.3390\/cimb47060464","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T05:52:47Z","timestamp":1750139567000},"page":"464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Reactive Oxygen Species as Key Molecules in the Pathogenesis of Alcoholic Fatty Liver Disease and Nonalcoholic Fatty Liver Disease: Future Perspectives"],"prefix":"10.3390","volume":"47","author":[{"given":"Zhiqing","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Chongqing Medical University, Yubei, Chongqing 401120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Chongqing Medical University, Yubei, Chongqing 401120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0265-5487","authenticated-orcid":false,"given":"Fei","family":"Han","sequence":"additional","affiliation":[{"name":"School of Public Health, Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Chongqing Medical University, Yubei, Chongqing 401120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41572-018-0014-7","article-title":"Alcoholic liver disease","volume":"4","author":"Seitz","year":"2018","journal-title":"Nat. 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