{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:43:03Z","timestamp":1785436983822,"version":"3.56.0"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"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":["U22A20517"],"award-info":[{"award-number":["U22A20517"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["U22A20517"],"award-info":[{"award-number":["U22A20517"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Hubei Province Project","award":["2024AFB926"],"award-info":[{"award-number":["2024AFB926"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Fish oil (FO) has been shown to confer beneficial effects on hepatic diseases in both humans and animals. This study aimed to investigate whether dietary fish oil (FO) supplementation alleviates deoxynivalenol (DON)-induced liver injury by modulating the ferroptosis signaling pathway in weaned piglets. Twenty-four weaned piglets were allocated to a 2 \u00d7 2 factorial design, with the main factors consisting of dietary treatment (5% corn oil or 5% FO supplementation) and DON exposure (basal diet or diet contaminated with 4 mg\/kg DON). After 21 days of dietary treatment, piglets were euthanized for collection of blood and liver samples. Dietary FO significantly attenuated DON-induced hepatic structural damage and inflammatory infiltration. Specifically, FO supplementation reduced the activities of aspartate transaminase (AST) and alkaline phosphatase (ALP), as well as the AST\/alanine aminotransferase (ALT) ratio following DON exposure. Dietary FO also decreased malondialdehyde (MDA) concentrations in both the liver and serum, lowered hepatic 4-hydroxynonenal (4-HNE) level and Fe2+ content, and increased hepatic glutathione (GSH) content. Moreover, dietary FO ameliorated ultrastructural liver damage induced by DON. Furthermore, DON significantly downregulated the mRNA levels of multiple genes associated with iron metabolism and ferroptosis, including heat shock protein beta-1 (HSPB1), acyl-CoA synthetase long chain family member 4 (ACSL4), and arachidonate 15-lipoxygenase (ALOX15), and upregulated the mRNA levels of transferrin (TF), ferritin heavy chain (FTH), solute carrier family 7 member 11 (SLC7A11), and transferrin receptor 1 (TFR1). Dietary FO counteracted these alterations by decreasing the mRNA of SLC7A11, TFR1, FTH, and TF after DON exposure. Finally, FO significantly decreased the protein expression of SLC7A11, iron-responsive element-binding protein 2 (IREB2), and FHT1 and increased the GPX4 protein expression following DON exposure. These findings suggest that FO may ameliorate DON-induced liver injury in weaned piglets, possibly through suppressing the ferroptosis signaling pathway.<\/jats:p>","DOI":"10.3390\/ani16081234","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T14:24:51Z","timestamp":1776435891000},"page":"1234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fish Oil Ameliorates Deoxynivalenol-Induced Liver Injury Through Modulating Ferroptosis Signaling Pathway in Weaned Pigs"],"prefix":"10.3390","volume":"16","author":[{"given":"Jiasi","family":"Liu","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minfang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Guo","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaokui","family":"Chen","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3320-2381","authenticated-orcid":false,"given":"Yulan","family":"Liu","sequence":"additional","affiliation":[{"name":"Hubei Key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109840","DOI":"10.1016\/j.foodres.2020.109840","article-title":"Gly-Pro-Ala peptide and FGSHF3 exert protective effects in DON-induced toxicity and intestinal damage via decreasing oxidative stress","volume":"139","author":"Deng","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"111373","DOI":"10.1016\/j.fct.2020.111373","article-title":"Effects of deoxynivalenol on the porcine growth performance and intestinal microbiota and potential remediation by a modified HSCAS binder","volume":"141","author":"Liu","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s40104-021-00603-0","article-title":"Occurrence of aflatoxin B 1, deoxynivalenol and zearalenone in feeds in China during 2018\u20132020","volume":"12","author":"Zhao","year":"2021","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.fct.2018.09.007","article-title":"Protective effects of Devosiasp. ANSB714 on growth performance, immunity function, antioxidant capacity and tissue residues in growing-finishing pigs fed with deoxynivalenol contaminated diets","volume":"121","author":"Li","year":"2018","journal-title":"Food Chem. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"111187","DOI":"10.1016\/j.fct.2020.111187","article-title":"Effect of deoxynivalenol on the porcine acquired immune response and potential remediation by a novel modified HSCAS adsorbent","volume":"138","author":"Zhang","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"112514","DOI":"10.1016\/j.fct.2021.112514","article-title":"Deoxynivalenol exposure induces liver damage in mice: Inflammation and immune responses, oxidative stress, and protective effects of Lactobacillus rhamnosus GG","volume":"156","author":"Bai","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.aninu.2021.11.009","article-title":"Cytochrome P450 enzymes mediated by DNA methylation is involved in deoxynivalenol-induced hepatoxicity in piglets","volume":"9","author":"Liu","year":"2022","journal-title":"Anim. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"112930","DOI":"10.1016\/j.fct.2022.112930","article-title":"Deoxynivalenol induces apoptosis and inflammation in the liver: Analysis using precision-cut liver slices","volume":"163","author":"Hasuda","year":"2022","journal-title":"Food Chem. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.fct.2014.06.027","article-title":"Role of oxidative stress in deoxynivalenol induced toxicity","volume":"72","author":"Mishra","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1080\/10408398.2015.1126549","article-title":"Anti-inflammatory effects of omega 3 and omega 6 polyunsaturated fatty acids in cardiovascular disease and metabolic syndrome","volume":"57","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12944-016-0190-y","article-title":"Fish oil alleviated high-fat diet-induced non-alcoholic fatty liver disease via regulating hepatic lipids metabolism and metaflammation: A transcriptomic study","volume":"15","author":"Yuan","year":"2016","journal-title":"Lipids Health Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s40104-015-0040-1","article-title":"Fatty acids, inflammation and intestinal health in pigs","volume":"6","author":"Liu","year":"2015","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41580-020-00324-8","article-title":"Ferroptosis: Mechanisms, biology, and role in disease","volume":"22","author":"Jiang","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s00011-022-01672-1","article-title":"Molecular mechanisms of ferroptosis and relevance to inflammation","volume":"72","author":"Deng","year":"2023","journal-title":"Inflamm. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wang, S., Yang, J., Zhang, B., Wu, K., Yang, A., Li, C., Zhang, J., Zhang, C., Rajput, S.A., and Zhang, N. (2018). Deoxynivalenol impairs porcine intestinal host defense peptide expression in weaned piglets and IPEC-J2 cells. Toxins, 10.","DOI":"10.3390\/toxins10120541"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"113811","DOI":"10.1016\/j.ecoenv.2022.113811","article-title":"Dihydroartemisinin alleviates deoxynivalenol induced liver apoptosis and inflammation in piglets","volume":"241","author":"Li","year":"2022","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s40104-024-01117-1","article-title":"Necroptosis contributes to deoxynivalenol-induced liver injury and inflammation in weaned piglets","volume":"15","author":"Xu","year":"2024","journal-title":"J. Anim. Sci. Biotech."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1177\/1753425912441955","article-title":"Dietary L-arginine supplementation alleviates liver injury caused by Escherichia coli LPS in weaned pigs","volume":"18","author":"Li","year":"2012","journal-title":"Innate Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1002\/hep.21626","article-title":"Omega-3 fatty acids alleviate chemically induced acute hepatitis by suppression of cytokines","volume":"45","author":"Weylandt","year":"2007","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1002\/jpen.2229","article-title":"Fish oil-based lipid emulsion alleviates parenteral nutrition-associated liver diseases and intestinal injury in piglets","volume":"46","author":"Chen","year":"2022","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1177\/1753425918821420","article-title":"Dietary fish oil supplementation alters liver gene expressions to protect against LPS-induced liver injury in weanling piglets","volume":"25","author":"Zhang","year":"2019","journal-title":"Innate Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.rvsc.2021.04.027","article-title":"Protective effect of glutamine and alanyl-glutamine against zearalenone-induced intestinal epithelial barrier dysfunction in IPEC-J2 cells","volume":"137","author":"Gu","year":"2021","journal-title":"Res. Vet. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1161\/CIRCRESAHA.120.316509","article-title":"Loss of cardiac ferritin H facilitates cardiomyopathy via slc7a11-mediated ferroptosis","volume":"127","author":"Fang","year":"2020","journal-title":"Circ. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1038\/s41418-020-00685-9","article-title":"Loss of ferroportin induces memory impairment by promoting ferroptosis in Alzheimer\u2019s disease","volume":"28","author":"Bao","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1038\/s41418-019-0299-4","article-title":"Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia\/reperfusion","volume":"26","author":"Li","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s40880-018-0288-x","article-title":"Amino acid transporter SLC7A11\/xCT at the crossroads of regulating redox homeostasis and nutrient dependency of cancer","volume":"38","author":"Koppula","year":"2018","journal-title":"Cancer Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5617","DOI":"10.1038\/onc.2015.32","article-title":"HSPB1 as a novel regulator of ferroptotic cancer cell death","volume":"34","author":"Sun","year":"2015","journal-title":"Oncogene"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s40104-023-00841-4","article-title":"Ferroptosis is involved in deoxynivalenol-induced intestinal damage in pigs","volume":"14","author":"Liu","year":"2023","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.cell.2012.03.042","article-title":"Ferroptosis: An iron-dependent form of nonapoptotic cell death","volume":"149","author":"Dixon","year":"2012","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1128\/MCB.00221-14","article-title":"Nrf2- and ATF4-dependent upregulation of xCT modulates the sensitivity of T24 bladder carcinoma cells to proteasome inhibition","volume":"34","author":"Ye","year":"2014","journal-title":"Mol. Cell. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature14344","article-title":"Ferroptosis as a p53-mediated activity during tumor suppression","volume":"520","author":"Jiang","year":"2015","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"44765","DOI":"10.1074\/jbc.M208704200","article-title":"Electrophile response element-mediated induction of the cystine\/glutamate exchange transporter gene expression","volume":"277","author":"Sasaki","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.cell.2017.09.021","article-title":"Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease","volume":"171","author":"Stockwell","year":"2017","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100876","DOI":"10.1016\/j.jlr.2025.100876","article-title":"DHA and EPA exacerbate hypoxia-induced ferroptosis in gastric and small intestinal mucosa by disrupting the balance between SLC7A11 upregulation and PUFA-PL accumulation","volume":"66","author":"Song","year":"2025","journal-title":"J. Lipid Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"108176","DOI":"10.1016\/j.meatsci.2020.108176","article-title":"Effects of dietary resveratrol supplementation in sows on antioxidative status, myofiber characteristic and meat quality of offspring","volume":"167","author":"Meng","year":"2020","journal-title":"Meat Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Hassan, M., Wang, Y., Rajput, S.A., Shaukat, A., Yang, P., Farooq, M.Z., Cheng, Q., Ali, M., Mi, X., and An, Y. (2023). Ameliorative effects of luteolin and activated charcoal on growth performance, immunity function, and antioxidant capacity in broiler chickens exposed to deoxynivalenol. Toxins, 15.","DOI":"10.3390\/toxins15080478"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Yang, Y., Wang, X., Chen, L., Wang, S., Han, J., Wang, Z., and Wen, M. (2023). A compared study of eicosapentaenoic acid and docosahexaenoic acid in improving seizure-induced cognitive deficiency in a pentylenetetrazol-kindling young mice model. Mar. Drugs, 21.","DOI":"10.3390\/md21090464"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e2200275","DOI":"10.1002\/mnfr.202200275","article-title":"DHA and EPA Prevent Seizure and Depression-Like Behavior by Inhibiting Ferroptosis and Neuroinflammation via Different Mode-of-Actions in a Pentylenetetrazole-Induced Kindling Model in Mice","volume":"66","author":"Wang","year":"2022","journal-title":"Mol. Nutr. Food Res."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/8\/1234\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:13:44Z","timestamp":1777004024000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/16\/8\/1234"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,17]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ani16081234"],"URL":"https:\/\/doi.org\/10.3390\/ani16081234","relation":{},"ISSN":["2076-2615"],"issn-type":[{"value":"2076-2615","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,17]]}}}