{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T05:27:33Z","timestamp":1786426053996,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Guangxi","award":["2024GXNSFAA999456"],"award-info":[{"award-number":["2024GXNSFAA999456"]}]},{"name":"Hunan Provincial Natural Science Foundation Regional Joint Fund Project","award":["2025JJ70435"],"award-info":[{"award-number":["2025JJ70435"]}]},{"name":"the National College Student Innovation and Entrepreneurship Training Program","award":["S202312214009, S202412214008"],"award-info":[{"award-number":["S202312214009, S202412214008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Sodium arsenite (SA) is an environmental chemical toxin that induces hepatotoxicity and cellular ferroptosis under exposure. Ferroptosis is characterized by elevated ferrous ion levels and decreased glutathione peroxidase 4 (GPX4) activity. Lentinan (LNT), a bioactive polysaccharide derived from shiitake mushrooms, was investigated for its regulatory effects on SA-induced hepatotoxicity. In vivo experiments demonstrated that LNT ameliorated SA-induced hepatic lipid accumulation, increased GPX4 content and the mRNA levels of AMP-activated protein kinase (AMPK), and decreased ferrous ion concentrations in the livers of mice. However, co-administration of the AMPK inhibitor compound C and LNT negated these protective effects on hepatic lipid accumulation and ferroptosis-related markers. Complementary in vitro studies revealed that LNT activates AMPK signaling, mimicking the antagonistic effects of the AMPK agonist metformin (Met) on lipid accumulation and ferroptosis in hepatocytes exposed to SA. Notably, immunoblotting analyses indicated that treatment with LNT or Met increased the LC3-II\/LC3-I ratio and upregulated the expression of ULK1 and the lipophagy receptor oxysterol-binding protein-related protein 8 (ORP8). Furthermore, co-immunoprecipitation assays demonstrated enhanced interaction between ORP8 and ULK1, suggesting activation of the AMPK-mediated ORP8\/ULK1 signaling pathway. This pathway appears to play a protective role against SA-induced hepatic lipid accumulation and ferroptosis. Collectively, these findings elucidate the beneficial effects of LNT-mediated AMPK activation in mitigating SA-induced lipid accumulation and ferroptosis in the liver.<\/jats:p>","DOI":"10.3390\/toxics14080701","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:00:43Z","timestamp":1786118443000},"page":"701","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lentinan Improves Sodium Arsenite-Induced Hepatic Lipid Accumulation and Ferroptosis: Role of AMPK Signaling Pathway"],"prefix":"10.3390","volume":"14","author":[{"given":"Shunli","family":"Luo","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, College of Public Health, Guilin Medical University, Guilin 541199, China"},{"name":"Department of Food Hygiene and Nutrition, College of Laboratory Medicine, Hunan University of Medicine, Huaihua 418000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yekang","family":"Deng","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, College of Public Health, Guilin Medical University, Guilin 541199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Lu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, College of Public Health, Guilin Medical University, Guilin 541199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2195-6138","authenticated-orcid":false,"given":"Yuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, College of Public Health, Guilin Medical University, Guilin 541199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref_1","unstructured":"National Toxicology Program (2011). 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