{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:05:17Z","timestamp":1790305517328,"version":"4.1.0"},"reference-count":45,"publisher":"SAGE Publications","issue":"10-11","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32102702"],"award-info":[{"award-number":["32102702"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Toxicol Ind Health"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is an escalating global health threat that has been linked to environmental pollutants such as the highly toxic dioxin-like congener 3,3\u2032,4,4\u2032,5-pentachlorobiphenyl (PCB 126). Although PCB 126 is known to impair hepatic function, the precise mechanisms\u2014particularly the contribution of ferroptosis, an iron-dependent, lipid-peroxidation-mediated form of cell death\u2014remain elusive. Here, we tested the hypothesis that ferroptosis underlies PCB 126\u2013induced NAFLD and delineated the key molecular pathways involved. Balb\/c mice were intraperitoneally injected with PCB 126 (1, 5, or 10\u00a0\u03bcM\/kg) for 14\u00a0days. Hepatic injury was assessed through serum biomarkers (ALT, AST, ALP), histopathology (H&amp;E and Oil Red O staining), and mitochondrial ultrastructure via transmission electron microscopy. Ferroptosis markers (GPX4, 4-HNE, Tf receptor), lipid peroxidation (MDA, GSH, SOD), iron homeostasis, and inflammatory cytokines (IL-1\u03b2, IL-6, TNF-\u03b1) were evaluated using qPCR, Western blotting, and ELISA. Results demonstrated that PCB 126 exposure induced NAFLD, evidenced by elevated liver-to-body weight ratios, serum liver enzymes, and steatosis. Ferroptosis was implicated through reduced mitochondrial cristae, suppressed GPX4 and SLC7A11 expression, increased lipid peroxidation, and iron accumulation. Additionally, PCB 126 activated the NF-\u03baB pathway, elevating pro-inflammatory cytokines and myeloperoxidase (MPO) activity, while oxidative stress was marked by NRF2\/KEAP1\/HO-1 axis disruption. In conclusion, PCB 126 promotes NAFLD in mice by triggering ferroptosis, inflammation, and oxidative stress. These findings highlight ferroptosis as a pivotal mechanistic link in PCB 126\u2013induced NAFLD, suggesting potential therapeutic targets for mitigating pollutant-driven liver injury.<\/jats:p>","DOI":"10.1177\/07482337251376455","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T08:52:51Z","timestamp":1758012771000},"page":"508-521","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Oxidative stress and ferroptosis mediate 3,3\u2032,4,4\u2032,5-pentachlorobiphenyl-induced non-alcoholic fatty liver disease in mice"],"prefix":"10.1177","volume":"41","author":[{"given":"Jingjing","family":"Wang","sequence":"first","affiliation":[{"name":"Chifeng Municipal Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yichun","family":"Chen","sequence":"additional","affiliation":[{"name":"Foshan University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanpeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Foshan University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingrong","family":"Ye","sequence":"additional","affiliation":[{"name":"Foshan University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Li","sequence":"additional","affiliation":[{"name":"Foshan University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5918-3644","authenticated-orcid":false,"given":"Ershun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Foshan University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"e_1_3_4_2_1","first-page":"137","article-title":"Environmental fate and global distribution of polychlorinated biphenyls","volume":"201","author":"Beyer A","year":"2009","unstructured":"Beyer A, Biziuk M (2009) Environmental fate and global distribution of polychlorinated biphenyls. 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