{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T03:23:31Z","timestamp":1791689011921,"version":"4.3.4"},"reference-count":69,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["NO.32072930"],"award-info":[{"award-number":["NO.32072930"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["NO.2022A1515110090"],"award-info":[{"award-number":["NO.2022A1515110090"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["NO.2023A1515012811"],"award-info":[{"award-number":["NO.2023A1515012811"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Boron compounds, classified as prohibited food additives due to their high toxicity, persist in pesticides and fertilisers, industrial processes, food supply chains, and consumer goods, perpetuating multisource exposure risks. Chronic ingestion may induce fatal hepatorenal injury; however, mechanistic insights and epidemiological surveillance remain critically lacking amidst sector-wide regulatory gaps. This study employed integrated cellular and organismal models to elucidate the relationship between boron-induced hepatotoxicity and ferroptosis. We demonstrate that dietary boron accumulation in chicken livers is associated with histopathological damage, mitochondrial cristae dissolution and atrophy (a hallmark of ferroptosis), and elevated serum biomarkers AST and ALT. Boron exacerbates oxidative damage in hepatocytes by elevating malondialdehyde (MDA) production while modulating the Nrf2\/ARE antioxidant signaling pathway\u2014specifically downregulating key genes (Nrf2, HO-1, GCLM, CAT). Concurrently, it inhibits critical antioxidant enzymes (SOD, T-AOC), thereby depleting cellular antioxidant defenses. Crucially, boron disrupts iron homeostasis and induces ferroptosis by dysregulating the SLC7A11-GPX4 pathway: upregulating pro-ferroptotic genes (ACSL4, TF, TFR) and downregulating cytoprotective genes (SLC7A11, GPX4, FTH1). Co-treatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1) attenuated boron-induced oxidative damage, whereas the ferroptosis inducer Erastin potentiated toxicity. Collectively, we pioneer the dual-pathogenic mechanism of boron hepatotoxicity\u2014oxidative stress and ferroptotic cell death\u2014establishing the SLC7A11\/GPX4 axis as a novel therapeutic target against boron toxicity.<\/jats:p>","DOI":"10.3390\/ani16050832","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T17:25:59Z","timestamp":1772817959000},"page":"832","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Boron Triggers Hepatic Ferroptosis: Unveiling the Dual-Pathogenic Nexus of Oxidative Stress and SLC7A11\/GPX4 Dysregulation"],"prefix":"10.3390","volume":"16","author":[{"given":"Ting","family":"He","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangli","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqian","family":"Su","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siying","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwen","family":"Quan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaolong","family":"Zhong","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghua","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"},{"name":"Laboratory Animal Center, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayou","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1460-9242","authenticated-orcid":false,"given":"Wenlan","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China"},{"name":"Laboratory Animal Center, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Brdar-Jokanovic, M. 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