{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T02:08:08Z","timestamp":1774922888175,"version":"3.50.1"},"reference-count":69,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNFSA210073688"],"award-info":[{"award-number":["NNFSA210073688"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jastro & Shields Graduate Research Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Objectives: This study utilized IPEC-J2, a neonatal pig jejunum-derived cell line, to assess how iron deficiency (ID) and excess (IE) alter enterocyte metabolism and the transcription of inflammatory markers. Methods: Cells were treated with deferiprone (DFP) or ferric ammonium citrate (FAC) to induce ID or IE, respectively. The study evaluated: (1) transcriptional changes in iron-regulatory genes over 96 h under ID or IE; (2) the interaction between iron imbalance and lipopolysaccharide (LPS) exposure on mRNA expression of inflammation markers and iron transporters; and (3) cellular metabolic responses to ID, IE, and iron repletion using untargeted metabolomics. Results: ID triggered dynamic transcriptional changes in iron regulatory genes and suppressed cellular proliferation via impaired DNA replication. IE resulted in a persistent reduction in TFRC expression. LPS increased CYBRD1 (p &lt; 0.001) and IL8 (p = 0.004) and tended to elevate TLR4 and TNF expression (p \u2264 0.07), while iron deficiency upregulated IL8 expression (p &lt; 0.001). ID disrupted the TCA cycle, reduced glucuronic acid synthesis, and elevated glycolysis for energy production, whereas IE increased cholesterol biosynthesis and decreased alpha-tocopherol levels. Repletion of iron partially reversed ID-induced metabolic changes. Conclusions: ID impaired enterocyte proliferation and profoundly disrupted cellular metabolism, whereas IE enhanced cholesterol synthesis and depleted alpha-tocopherol levels. Restoration of cellular metabolism following iron repletion was observed, highlighting the resilience of enterocytes.<\/jats:p>","DOI":"10.3390\/metabo15110691","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T05:48:46Z","timestamp":1761716926000},"page":"691","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Iron Stress Reprograms Enterocyte Metabolism"],"prefix":"10.3390","volume":"15","author":[{"given":"Shya E.","family":"Navazesh","sequence":"first","affiliation":[{"name":"Department of Nutrition, University of California Davis, 1 Shields Ave., Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7447-5688","authenticated-orcid":false,"given":"Peng","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of California Davis, 1 Shields Ave., Davis, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"ref_1","first-page":"164","article-title":"Review on iron and its importance for human health","volume":"19","author":"Abbaspour","year":"2014","journal-title":"J. Res. Med. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e178","DOI":"10.1093\/nutrit\/nuae063","article-title":"Prevalence and Determinants of Stunting-Anemia and Wasting-Anemia Comorbidities and Micronutrient Deficiencies in Children Under 5 in the Least-Developed Countries: A Systematic Review and Meta-analysis","volume":"83","author":"Dessie","year":"2025","journal-title":"Nutr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s12098-010-0120-3","article-title":"Iron deficiency and infection","volume":"77","author":"Kumar","year":"2010","journal-title":"Indian J. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"616S","DOI":"10.1093\/jn\/131.2.616S","article-title":"Iron and its relation to immunity and infectious disease","volume":"131","author":"Oppenheimer","year":"2001","journal-title":"J. Nutr."},{"key":"ref_5","unstructured":"(2016). WHO Guidelines Approved by the Guidelines Review Committee. Guideline: Daily Iron Supplementation in Infants and Children, World Health Organization."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1093\/jn\/132.11.3249","article-title":"Iron supplementation affects growth and morbidity of breast-fed infants: Results of a randomized trial in Sweden and Honduras","volume":"132","author":"Dewey","year":"2002","journal-title":"J. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.mam.2005.07.001","article-title":"Iron, oxidative stress and human health","volume":"26","author":"Puntarulo","year":"2005","journal-title":"Mol. Aspects Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.3945\/ajcn.110.004564","article-title":"The effects of iron fortification on the gut microbiota in African children: A randomized controlled trial in Cote d\u2019Ivoire","volume":"92","author":"Zimmermann","year":"2010","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nri3608","article-title":"Intestinal epithelial cells: Regulators of barrier function and immune homeostasis","volume":"14","author":"Peterson","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40348-016-0048-4","article-title":"The cross-talk between enterocytes and intraepithelial lymphocytes","volume":"3","author":"Vitale","year":"2016","journal-title":"Mol. Cell. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.molmed.2011.05.011","article-title":"Enterocyte death and intestinal barrier maintenance in homeostasis and disease","volume":"17","author":"Vereecke","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/0026-0495(88)90179-5","article-title":"Glucose, glutamine, and ketone-body metabolism in human enterocytes","volume":"37","author":"Ashy","year":"1988","journal-title":"Metabolism"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1007\/s003840000258","article-title":"Bidirectional supply of glutamine maintains enterocyte ATP content in the in vitro using chamber model","volume":"15","author":"Yang","year":"2000","journal-title":"Int. J. Colorectal Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6886","DOI":"10.1038\/s41467-022-34687-7","article-title":"Enterotoxigenic Escherichia coli heat-labile toxin drives enteropathic changes in small intestinal epithelia","volume":"13","author":"Sheikh","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1136\/gut.2003.027540","article-title":"Arginine stimulates intestinal cell migration through a focal adhesion kinase dependent mechanism","volume":"53","author":"Rhoads","year":"2004","journal-title":"Gut"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1053\/j.gastro.2008.12.002","article-title":"Glutamine increases autophagy under Basal and stressed conditions in intestinal epithelial cells","volume":"136","author":"Sakiyama","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1007\/s00726-009-0334-8","article-title":"L-Arginine stimulates proliferation and prevents endotoxin-induced death of intestinal cells","volume":"38","author":"Tan","year":"2010","journal-title":"Amino Acids"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"501","DOI":"10.3945\/jn.115.224857","article-title":"L-Glutamine Enhances Tight Junction Integrity by Activating CaMK Kinase 2-AMP-Activated Protein Kinase Signaling in Intestinal Porcine Epithelial Cells","volume":"146","author":"Wang","year":"2016","journal-title":"J. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Perng, V., Navazesh, S.E., Park, J., Arballo, J.R., and Ji, P. (2022). Iron Deficiency and Overload Modulate the Inflammatory Responses and Metabolism of Alveolar Macrophages. Nutrients, 14.","DOI":"10.3390\/nu14153100"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jtemb.2018.01.002","article-title":"Oral administration of liquid iron preparation containing excess iron induces intestine and liver injury, impairs intestinal barrier function and alters the gut microbiota in rats","volume":"47","author":"Fang","year":"2018","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.3945\/jn.116.231621","article-title":"Dietary Iron Deficiency and Oversupplementation Increase Intestinal Permeability, Ion Transport, and Inflammation in Pigs","volume":"146","author":"Li","year":"2016","journal-title":"J. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/s41419-021-03559-1","article-title":"The emerging role of ferroptosis in intestinal disease","volume":"12","author":"Xu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1053\/gast.2001.24843","article-title":"PKC-delta inhibits anchorage-dependent and -independent growth, enhances differentiation, and increases apoptosis in CaCo-2 cells","volume":"120","author":"Cerda","year":"2001","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Vergauwen, H. (2015). The IPEC-J2 Cell Line. The Impact of Food Bioactives on Health: In Vitro and Ex Vivo Models, Springer.","DOI":"10.1007\/978-3-319-16104-4_12"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e0132323","DOI":"10.1371\/journal.pone.0132323","article-title":"Comparing Two Intestinal Porcine Epithelial Cell Lines (IPECs): Morphological Differentiation, Function and Metabolism","volume":"10","author":"Nossol","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1093\/jn\/nxz166","article-title":"Excess Iron Enhances Purine Catabolism Through Activation of Xanthine Oxidase and Impairs Myelination in the Hippocampus of Nursing Piglets","volume":"149","author":"Ji","year":"2019","journal-title":"J. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"30.34.31","DOI":"10.1002\/0471142727.mb3004s114","article-title":"Metabolomics by Gas Chromatography-Mass Spectrometry: Combined Targeted and Untargeted Profiling","volume":"114","author":"Fiehn","year":"2016","journal-title":"Curr. Protoc. Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1111\/j.1365-313X.2007.03387.x","article-title":"Quality control for plant metabolomics: Reporting MSI-compliant studies","volume":"53","author":"Fiehn","year":"2008","journal-title":"Plant J."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Fiehn, O., Wohlgemuth, G., and Scholz, M. (2005). Setup and Annotation of Metabolomic Experiments by Integrating Biological and Mass Spectrometric Metadata. Data Integration in the Life Sciences, Proceedings of the Second International Workshop, DILS 2005, San Diego, CA, USA, 20\u201322 July 2005, Springer.","DOI":"10.1007\/11530084_18"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.micinf.2005.04.003","article-title":"The role of enterocytes in the intestinal barrier function and antigen uptake","volume":"7","author":"Snoeck","year":"2005","journal-title":"Microbes Infect."},{"key":"ref_31","first-page":"239","article-title":"A Review on Iron Chelators in Treatment of Iron Overload Syndromes","volume":"10","author":"Mobarra","year":"2016","journal-title":"Int. J. Hematol. Oncol. Stem Cell Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1172\/JCI38499","article-title":"HIF-2alpha, but not HIF-1alpha, promotes iron absorption in mice","volume":"119","author":"Mastrogiannaki","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.cmet.2008.12.012","article-title":"Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency","volume":"9","author":"Shah","year":"2009","journal-title":"Cell Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1053\/j.gastro.2011.03.007","article-title":"Hypoxia-inducible factor-2\u03b1 mediates the adaptive increase of intestinal ferroportin during iron deficiency in mice","volume":"140","author":"Taylor","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"G635","DOI":"10.1152\/ajpgi.00160.2015","article-title":"Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese","volume":"309","author":"Shawki","year":"2015","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"42579","DOI":"10.1074\/jbc.M207918200","article-title":"Multiple, conserved iron-responsive elements in the 3\u2032-untranslated region of transferrin receptor mRNA enhance binding of iron regulatory protein 2","volume":"277","author":"Erlitzki","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"102147","DOI":"10.1016\/j.cdnut.2024.102147","article-title":"Iron Fortification and Inulin Supplementation in Early Infancy: Evaluating the Impact on Iron Metabolism and Trace Mineral Status in a Piglet Model","volume":"8","author":"Park","year":"2024","journal-title":"Curr. Dev. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/jn\/nxaa326","article-title":"Iron Deficiency and Iron Excess Differently Affect Dendritic Architecture of Pyramidal Neurons in the Hippocampus of Piglets","volume":"151","author":"Perng","year":"2021","journal-title":"J. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.aninu.2024.05.006","article-title":"New insights into the mechanisms of iron absorption: Iron dextran uptake in the intestines of weaned pigs through glucose transporter 5 (GLUT5) and divalent metal transporter 1 (DMT1) transporters","volume":"19","author":"Deng","year":"2024","journal-title":"Anim. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0014-5793(01)03189-1","article-title":"Iron-dependent regulation of the divalent metal ion transporter","volume":"509","author":"Gunshin","year":"2001","journal-title":"FEBS Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1093\/jn\/132.4.693","article-title":"Iron treatment downregulates DMT1 and IREG1 mRNA expression in Caco-2 cells","volume":"132","author":"Martini","year":"2002","journal-title":"J. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"G1070","DOI":"10.1152\/ajpgi.2000.279.5.G1070","article-title":"Dietary iron induces rapid changes in rat intestinal divalent metal transporter expression","volume":"279","author":"Yeh","year":"2000","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4406","DOI":"10.1182\/blood.V93.12.4406","article-title":"Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron","volume":"93","author":"Gruenheid","year":"1999","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1006\/bcmd.1998.0186","article-title":"The human Nramp2 gene: Characterization of the gene structure, alternative splicing, promoter region and polymorphisms","volume":"24","author":"Lee","year":"1998","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/s12276-024-01180-8","article-title":"Hypoxia, oxidative stress, and the interplay of HIFs and NRF2 signaling in cancer","volume":"56","author":"Bae","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.cmet.2015.09.006","article-title":"Ironing out Ferroportin","volume":"22","author":"Drakesmith","year":"2015","journal-title":"Cell Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3389\/fvets.2018.00242","article-title":"Emerging Regulatory Role of Nrf2 in Iron, Heme, and Hemoglobin Metabolism in Physiology and Disease","volume":"5","author":"Kasai","year":"2018","journal-title":"Front. Vet. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4802","DOI":"10.1038\/s41598-019-39214-1","article-title":"Deferiprone: Pan-selective Histone Lysine Demethylase Inhibition Activity and Structure Activity Relationship Study","volume":"9","author":"Khodaverdian","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"103727","DOI":"10.1016\/j.redox.2025.103727","article-title":"Revised model for cell cycle regulation by iron: Differential roles between transferrin and ferritin","volume":"85","author":"Yanagiya","year":"2025","journal-title":"Redox Biol."},{"key":"ref_50","first-page":"755","article-title":"Cytotoxic activity of deferiprone, maltol and related hydroxyketones against human tumor cell lines","volume":"24","author":"Yasumoto","year":"2004","journal-title":"Anticancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.cimid.2008.08.003","article-title":"Innate immune activation of swine intestinal epithelial cell lines (IPEC-J2 and IPI-2I) in response to LPS from Salmonella typhimurium","volume":"33","author":"Arce","year":"2010","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s00709-023-01920-z","article-title":"HIF-1\u03b1 is an important regulator of IL-8 expression in human bone marrow stromal cells under hypoxic microenvironment","volume":"261","author":"Huang","year":"2024","journal-title":"Protoplasma"},{"key":"ref_53","first-page":"5822","article-title":"Hypoxia-induced elevation in interleukin-8 expression by human ovarian carcinoma cells","volume":"59","author":"Xu","year":"1999","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e61050","DOI":"10.1371\/journal.pone.0061050","article-title":"Role of hepcidin in the setting of hypoferremia during acute inflammation","volume":"8","author":"Deschemin","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14712\/fb2006052010001","article-title":"Effect of lipopolysaccharide and bleeding on the expression of intestinal proteins involved in iron and haem transport","volume":"52","author":"Krijt","year":"2006","journal-title":"Folia Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1172\/JCI122359","article-title":"Hepatic hepcidin\/intestinal HIF-2\u03b1 axis maintains iron absorption during iron deficiency and overload","volume":"129","author":"Schwartz","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Paneque, A., Fortus, H., Zheng, J., Werlen, G., and Jacinto, E. (2023). The Hexosamine Biosynthesis Pathway: Regulation and Function. Genes, 14.","DOI":"10.3390\/genes14040933"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0005-2728(99)00088-2","article-title":"Iron-dependent changes in cellular energy metabolism: Influence on citric acid cycle and oxidative phosphorylation","volume":"1413","author":"Oexle","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1194\/jlr.M200363-JLR200","article-title":"Deficiency in ethanolamine plasmalogen leads to altered cholesterol transport","volume":"44","author":"Munn","year":"2003","journal-title":"J. Lipid Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.bbalip.2017.12.003","article-title":"Distinct lipidomic profiles in models of physiological and pathological cardiac remodeling, and potential therapeutic strategies","volume":"1863","author":"Tham","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e82210","DOI":"10.7554\/eLife.82210","article-title":"Ether lipid biosynthesis promotes lifespan extension and enables diverse pro-longevity paradigms in Caenorhabditis elegans","volume":"12","author":"Cedillo","year":"2023","journal-title":"eLife"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.devcel.2020.06.019","article-title":"Dietary Lipids Induce Ferroptosis in Caenorhabditiselegans and Human Cancer Cells","volume":"54","author":"Perez","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/s41586-020-2732-8","article-title":"Plasticity of ether lipids promotes ferroptosis susceptibility and evasion","volume":"585","author":"Zou","year":"2020","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1515364","DOI":"10.3389\/fmicb.2025.1515364","article-title":"Energy metabolism and the intestinal barrier: Implications for understanding and managing intestinal diseases","volume":"16","author":"Chen","year":"2025","journal-title":"Front. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e157","DOI":"10.18295\/2075-0528.1566","article-title":"The role of vitamin E in human health and some diseases","volume":"14","author":"Rizvi","year":"2014","journal-title":"Sultan Qaboos Univ. Med. J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.biopha.2005.06.005","article-title":"Alpha-tocopherol: Roles in prevention and therapy of human disease","volume":"59","author":"Tucker","year":"2005","journal-title":"Biomed. Pharmacother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41419-021-04008-9","article-title":"GPX4 and vitamin E cooperatively protect hematopoietic stem and progenitor cells from lipid peroxidation and ferroptosis","volume":"12","author":"Hu","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"103303","DOI":"10.1016\/j.redox.2024.103303","article-title":"Vitamin E and GPX4 cooperatively protect treg cells from ferroptosis and alleviate intestinal inflammatory damage in necrotizing enterocolitis","volume":"75","author":"Luo","year":"2024","journal-title":"Redox Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"101156","DOI":"10.1016\/j.jbc.2021.101156","article-title":"Iron loading induces cholesterol synthesis and sensitizes endothelial cells to TNF\u03b1-mediated apoptosis","volume":"297","author":"Fisher","year":"2021","journal-title":"J. Biol. Chem."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/11\/691\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T06:21:20Z","timestamp":1761718880000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/15\/11\/691"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,24]]},"references-count":69,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["metabo15110691"],"URL":"https:\/\/doi.org\/10.3390\/metabo15110691","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,24]]}}}