{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:25:56Z","timestamp":1790241956473,"version":"4.1.0"},"reference-count":189,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,2,28]],"date-time":"2020-02-28T00:00:00Z","timestamp":1582848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ferroptosis has emerged as a new type of cell death in different pathological conditions, including neurological and kidney diseases and, especially, in different types of cancer. The hallmark of this regulated cell death is the presence of iron-driven lipid peroxidation; the activation of key genes related to this process such as glutathione peroxidase-4 (gpx4), acyl-CoA synthetase long-chain family member-4 (acsl4), carbonyl reductase [NADPH] 3 (cbr3), and prostaglandin peroxidase synthase-2 (ptgs2); and morphological changes including shrunken and electron-dense mitochondria. Iron overload in the liver has long been recognized as both a major trigger of liver damage in different diseases, and it is also associated with liver fibrosis. New evidence suggests that ferroptosis might be a novel type of non-apoptotic cell death in several liver diseases including non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), drug-induced liver injury (DILI), viral hepatitis, and hemochromatosis. The interaction between iron-related lipid peroxidation, cellular stress signals, and antioxidant systems plays a pivotal role in the development of this novel type of cell death. In addition, integrated responses from lipidic mediators together with free iron from iron-containing enzymes are essential to understanding this process. The presence of ferroptosis and the exact mechanisms leading to this non-apoptotic type of cell death in the liver remain scarcely elucidated. Recognizing ferroptosis as a novel type of cell death in the liver could lead to the understanding of the complex interaction between different types of cell death, their role in progression of liver fibrosis, the development of new biomarkers, as well as the use of modulators of ferroptosis, allowing improved theranostic approaches in the clinic.<\/jats:p>","DOI":"10.3390\/ijms21051651","type":"journal-article","created":{"date-parts":[[2020,3,3]],"date-time":"2020-03-03T03:13:28Z","timestamp":1583205208000},"page":"1651","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["Reclassifying Hepatic Cell Death during Liver Damage: Ferroptosis\u2014A Novel Form of Non-Apoptotic Cell Death?"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7637-4477","authenticated-orcid":false,"given":"Ricardo U.","family":"Mac\u00edas-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City 14080, Mexico"},{"name":"Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany"},{"name":"MICTL\u00c1N-Network (Mechanisms of Liver Injury, Cell Death and Translational Nutrition in Liver Diseases Research Network), Mexico City 14080, Mexico"},{"name":"Liver Fibrosis and Nutrition Lab (LFN Lab), Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Eugenia","family":"Inzaugarat","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany"},{"name":"MICTL\u00c1N-Network (Mechanisms of Liver Injury, Cell Death and Translational Nutrition in Liver Diseases Research Network), Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Ruiz-Marg\u00e1in","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City 14080, Mexico"},{"name":"Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany"},{"name":"MICTL\u00c1N-Network (Mechanisms of Liver Injury, Cell Death and Translational Nutrition in Liver Diseases Research Network), Mexico City 14080, Mexico"},{"name":"Liver Fibrosis and Nutrition Lab (LFN Lab), Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4197-4843","authenticated-orcid":false,"given":"Leonard J.","family":"Nelson","sequence":"additional","affiliation":[{"name":"Institute for Bioengineering (IBioE), School of Engineering, Faraday Building, The University of Edinburgh, Edinburgh EH9 3 JL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Trautwein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1499-650X","authenticated-orcid":false,"given":"Francisco Javier","family":"Cubero","sequence":"additional","affiliation":[{"name":"MICTL\u00c1N-Network (Mechanisms of Liver Injury, Cell Death and Translational Nutrition in Liver Diseases Research Network), Mexico City 14080, Mexico"},{"name":"Department of Immunology, Ophthalmology &amp; ENT, Complutense University School of Medicine, 28040 Madrid, Spain"},{"name":"12 de Octubre Health Research Institute (imas12), 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1053\/gast.2002.36061","article-title":"AGA technical review on the evaluation of liver chemistry tests","volume":"123","author":"Green","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1001\/jama.2015.5370","article-title":"Nonalcoholic fatty liver disease: A systematic review","volume":"313","author":"Rinella","year":"2015","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1478-3231.2005.01028.x","article-title":"Decreased risk of hepatocellular carcinoma in patients with chronic hepatitis C whose serum alanine aminotransferase levels became less than twice the upper limit of normal following interferon therapy","volume":"25","author":"Moriyama","year":"2005","journal-title":"Liver Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1111\/j.1365-2036.2006.03113.x","article-title":"Persistent elevation of serum alanine aminotransferase levels leads to poor survival and hepatocellular carcinoma development in type 1 autoimmune hepatitis","volume":"24","author":"Miyake","year":"2006","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.jhep.2013.12.026","article-title":"Biomarkers of liver cell death","volume":"60","author":"Eguchi","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1053\/j.gastro.2014.07.018","article-title":"Cell death and cell death responses in liver disease: Mechanisms and clinical relevance","volume":"147","author":"Luedde","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.cellsig.2014.11.038","article-title":"Molecular mechanisms of hepatic apoptosis regulated by nuclear factors","volume":"27","author":"Wang","year":"2015","journal-title":"Cell. Signal."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1002\/hep.26592","article-title":"NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation, and fibrosis in mice","volume":"59","author":"Wree","year":"2014","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1152\/physrev.00061.2009","article-title":"Hepatocyte death: A clear and present danger","volume":"90","author":"Malhi","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature14344","article-title":"Ferroptosis as a p53-mediated activity during tumour suppression","volume":"520","author":"Jiang","year":"2015","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.nbd.2016.05.011","article-title":"Ferroptosis, a newly characterized form of cell death in Parkinson\u2019s disease that is regulated by PKC","volume":"94","author":"Gouel","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"16836","DOI":"10.1073\/pnas.1415518111","article-title":"Synchronized renal tubular cell death involves ferroptosis","volume":"111","author":"Linkermann","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/ncb3064","article-title":"Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice","volume":"16","author":"Schneider","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"521","DOI":"10.3748\/wjg.v25.i5.521","article-title":"Iron and liver fibrosis: Mechanistic and clinical aspects","volume":"25","author":"Mehta","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.jhep.2008.11.011","article-title":"Iron in NASH, chronic liver diseases and HCC: How much iron is too much?","volume":"50","author":"Pietrangelo","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"26087","DOI":"10.3390\/ijms161125942","article-title":"The Role of Oxidative Stress and Antioxidants in Liver Diseases","volume":"16","author":"Li","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death 2018","volume":"25","author":"Galluzzi","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nri.2015.7","article-title":"Converging roles of caspases in inflammasome activation, cell death and innate immunity","volume":"16","author":"Man","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1056\/NEJMra0901217","article-title":"Cell Death","volume":"361","author":"Hotchkiss","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1038\/cdd.2017.65","article-title":"Initiation and execution mechanisms of necroptosis: An overview","volume":"24","author":"Grootjans","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/nature14191","article-title":"Necroptosis and its role in inflammation","volume":"517","author":"Pasparakis","year":"2015","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1053\/j.gastro.2008.05.055","article-title":"Acute Liver Cell Damage in Patients With Anorexia Nervosa: A Possible Role of Starvation-Induced Hepatocyte Autophagy","volume":"135","author":"Rautou","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"R568","DOI":"10.1016\/j.cub.2016.02.019","article-title":"Pyroptosis","volume":"26","author":"Lamkanfi","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"aaf2154","DOI":"10.1126\/science.aaf2154","article-title":"Programmed necrosis in inflammation: Toward identification of the effector molecules","volume":"352","author":"Wallach","year":"2016","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nature18590","article-title":"Pore-forming activity and structural autoinhibition of the gasdermin family","volume":"535","author":"Ding","year":"2016","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.cell.2011.10.026","article-title":"Autophagy: Renovation of cells and tissues","volume":"147","author":"Mizushima","year":"2011","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/nrgastro.2016.185","article-title":"Autophagy in the liver: Functions in health and disease","volume":"14","author":"Ueno","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nri.2016.100","article-title":"Crosstalk between autophagy and inflammatory signalling pathways: Balancing defence and homeostasis","volume":"16","author":"Cadwell","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1056\/NEJMra1205406","article-title":"Autophagy in human health and disease","volume":"368","author":"Choi","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/s41418-018-0252-y","article-title":"Autophagy-dependent cell death","volume":"26","author":"Denton","year":"2019","journal-title":"Cell Death Differ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"E4966","DOI":"10.1073\/pnas.1603244113","article-title":"Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis","volume":"113","author":"Yang","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/cdd.2015.158","article-title":"Ferroptosis: Process and function","volume":"23","author":"Xie","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1136\/gut.2004.053850","article-title":"Apoptosis: A mechanism of acute and chronic liver injury","volume":"54","author":"Guicciardi","year":"2005","journal-title":"Gut"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e996","DOI":"10.1038\/cddis.2013.499","article-title":"Molecular mechanisms of hepatic apoptosis","volume":"5","author":"Wang","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nrm2312","article-title":"Apoptosis: Controlled demolition at the cellular level","volume":"9","author":"Taylor","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1053\/jhep.2003.50472","article-title":"Kupffer cell engulfment of apoptotic bodies stimulates death ligand and cytokine expression","volume":"38","author":"Canbay","year":"2003","journal-title":"Hepatology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0092-8674(04)00046-7","article-title":"Cell death: Critical control points","volume":"116","author":"Danial","year":"2004","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nrm3722","article-title":"Control of apoptosis by the BCL-2 protein family: Implications for physiology and therapy","volume":"15","author":"Czabotar","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1126\/science.275.5302.983","article-title":"Structure of Bcl-xL-Bak peptide complex: Recognition between regulators of apoptosis","volume":"275","author":"Sattler","year":"1997","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1126\/science.281.5381.1309","article-title":"Mitochondria and apoptosis","volume":"281","author":"Green","year":"1998","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1038\/sj.cdd.4401963","article-title":"Mitochondrial outer membrane permeabilization during apoptosis: The innocent bystander scenario","volume":"13","author":"Chipuk","year":"2006","journal-title":"Cell Death Differ."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/sj.cdd.4402028","article-title":"Apoptosome: A platform for the activation of initiator caspases","volume":"14","author":"Bao","year":"2007","journal-title":"Cell Death Differ."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/nrm2434","article-title":"Cytochrome c: Functions beyond respiration","volume":"9","author":"Ow","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nrm2153","article-title":"The apoptosome: Signalling platform of cell death","volume":"8","author":"Riedl","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/ni.1714","article-title":"Death receptor signal transducers: Nodes of coordination in immune signaling networks","volume":"10","author":"Wilson","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1038\/nature07606","article-title":"The Fas-FADD death domain complex structure unravels signalling by receptor clustering","volume":"457","author":"Scott","year":"2009","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nri.2016.76","article-title":"Cell death and immunity: Gasdermins: The hole picture emerges","volume":"16","author":"Bordon","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/386517a0","article-title":"Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors","volume":"386","author":"Thome","year":"1997","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/nrm.2016.149","article-title":"Necroptosis in development, inflammation and disease","volume":"18","author":"Weinlich","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1146\/annurev-pathol-052016-100247","article-title":"Necroptosis: Mechanisms and Relevance to Disease","volume":"12","author":"Galluzzi","year":"2017","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.ymeth.2007.12.001","article-title":"Apoptosis and necrosis: Detection, discrimination and phagocytosis","volume":"44","author":"Krysko","year":"2008","journal-title":"Methods"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Tomaipitinca, L., Mandatori, S., Mancinelli, R., Giulitti, F., Petrungaro, S., Moresi, V., Facchiano, A., Ziparo, E., Gaudio, E., and Giampietri, C. (2019). The Role of Autophagy in Liver Epithelial Cells and Its Impact on Systemic Homeostasis. Nutrients, 11.","DOI":"10.3390\/nu11040827"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/nature06639","article-title":"Autophagy fights disease through cellular self-digestion","volume":"451","author":"Mizushima","year":"2008","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"149","DOI":"10.4161\/auto.3631","article-title":"Permeases recycle amino acids resulting from autophagy","volume":"3","author":"Yang","year":"2007","journal-title":"Autophagy"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1038\/ncb1192","article-title":"Role of Bcl-2 family proteins in a non-apoptopic programmed cell death dependent on autophagy genes","volume":"6","author":"Shimizu","year":"2004","journal-title":"Nat. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1080\/15548627.2016.1187366","article-title":"Autophagy promotes ferroptosis by degradation of ferritin","volume":"12","author":"Hou","year":"2016","journal-title":"Autophagy"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Santana-Codina, N., and Mancias, J.D. (2018). The role of NCOA4-mediated ferritinophagy in health and disease. Pharmaceuticals, 11.","DOI":"10.20944\/preprints201809.0148.v1"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1056\/NEJMra1004967","article-title":"Iron overload in human disease","volume":"366","author":"Fleming","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cell.2010.06.028","article-title":"Two to tango: Regulation of Mammalian iron metabolism","volume":"142","author":"Hentze","year":"2010","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1182\/blood-2013-06-427757","article-title":"The liver: Conductor of systemic iron balance","volume":"123","author":"Meynard","year":"2014","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1172\/JCI67225","article-title":"Iron regulation by hepcidin","volume":"123","author":"Zhao","year":"2013","journal-title":"J. Clin. Invest."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1182\/blood-2018-06-815894","article-title":"Liver iron sensing and body iron homeostasis","volume":"133","author":"Wang","year":"2019","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/nri3863","article-title":"Iron homeostasis in host defence and inflammation","volume":"15","author":"Ganz","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.bbrc.2016.10.086","article-title":"Lipid peroxidation in cell death","volume":"482","author":"Gaschler","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1038\/cdd.2013.138","article-title":"Cell death and diseases related to oxidative stress: 4-hydroxynonenal (HNE) in the balance","volume":"20","author":"Dalleau","year":"2013","journal-title":"Cell Death Differ."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cmet.2008.07.005","article-title":"Glutathione peroxidase 4 senses and translates oxidative stress into 12\/15-lipoxygenase dependent- and AIF-mediated cell death","volume":"8","author":"Seiler","year":"2008","journal-title":"Cell Metab."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Feng, H., and Stockwell, B.R. (2018). Unsolved mysteries: How does lipid peroxidation cause ferroptosis?. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.2006203"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.chembiol.2015.11.016","article-title":"Cell-Line Selectivity Improves the Predictive Power of Pharmacogenomic Analyses and Helps Identify NADPH as Biomarker for Ferroptosis Sensitivity","volume":"23","author":"Shimada","year":"2016","journal-title":"Cell Chem. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"11455","DOI":"10.1074\/jbc.274.17.11455","article-title":"Cloning and expression of a plasma membrane cystine\/glutamate exchange transporter composed of two distinct proteins","volume":"274","author":"Sato","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.cmet.2013.02.004","article-title":"Iron and copper in mitochondrial diseases","volume":"17","author":"Xu","year":"2013","journal-title":"Cell Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"568S","DOI":"10.1093\/jn\/131.2.568S","article-title":"Iron Biology in Immune Function, Muscle Metabolism and Neuronal Functioning","volume":"131","author":"Beard","year":"2001","journal-title":"J. Nutr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1016\/j.bbagen.2012.11.020","article-title":"Glutathione peroxidases","volume":"1830","author":"Maiorino","year":"2013","journal-title":"Biochim. Biophys. Acta - Gen. Subj."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/hep.29117","article-title":"Characterization of ferroptosis in murine models of hemochromatosis","volume":"66","author":"Wang","year":"2017","journal-title":"Hepatology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e02523","DOI":"10.7554\/eLife.02523","article-title":"Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis","volume":"3","author":"Dixon","year":"2014","journal-title":"Elife"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1158\/1541-7786.MCR-18-0055","article-title":"Ferroptosis-induced endoplasmic reticulum stress: Cross-talk between ferroptosis and apoptosis","volume":"16","author":"Lee","year":"2018","journal-title":"Mol. Cancer Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/S0022-2275(20)39187-2","article-title":"Fatty acids as signal transducing molecules: Involvement in the differentiation of preadipose to adipose cells","volume":"35","author":"Amri","year":"1994","journal-title":"J. Lipid Res."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"De Carvalho, C.C.C.R., and Caramujo, M.J. (2018). The various roles of fatty acids. Molecules, 23.","DOI":"10.3390\/molecules23102583"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1007\/BF02637048","article-title":"Effects of different polunsaturated fatty acids on growth-related early gene expression and cell growth","volume":"31","author":"Sellmayer","year":"1996","journal-title":"Lipids"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1172\/JCI13210","article-title":"Arachidonic acid as a bioactive molecule","volume":"107","author":"Brash","year":"2001","journal-title":"J. Clin. Invest."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5241","DOI":"10.1073\/pnas.93.11.5241","article-title":"Arachidonate lipoxygenases as essential regulators of cell survival and apoptosis","volume":"93","author":"Tang","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1038\/cdd.2016.25","article-title":"Emerging roles for lipids in non-apoptotic cell death","volume":"23","author":"Magtanong","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nm.3516","article-title":"Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2","volume":"20","author":"Fullerton","year":"2014","journal-title":"Nat. Med."},{"key":"ref_85","first-page":"3299","article-title":"The Cap\u2019n\u2019Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45-related factor 2) controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes","volume":"61","author":"McMahon","year":"2001","journal-title":"Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.tips.2013.04.005","article-title":"Toward clinical application of the Keap1-Nrf2 pathway","volume":"34","author":"Suzuki","year":"2013","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.freeradbiomed.2015.07.155","article-title":"Vorinostat synergizes with EGFR inhibitors in NSCLC cells by increasing ROS via up-regulation of the major mitochondrial porin VDAC1 and modulation of the c-Myc-NRF2-KEAP1 pathway","volume":"89","author":"Leone","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1073\/pnas.0308347100","article-title":"Scaffolding of Keap1 to the actin cytoskeleton controls the function of Nrf2 as key regulator of cytoprotective phase 2 genes","volume":"101","author":"Kang","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1006\/bbrc.1997.6943","article-title":"An Nrf2\/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements","volume":"236","author":"Itoh","year":"1997","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.chembiol.2017.06.009","article-title":"\u03b2-TrCP1 Is a Vacillatory Regulator of Wnt Signaling","volume":"24","author":"Long","year":"2017","journal-title":"Cell Chem. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.freeradbiomed.2012.06.023","article-title":"Validation of the multiple sensor mechanism of the Keap1-Nrf2 system","volume":"53","author":"Takaya","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1128\/MCB.00868-15","article-title":"Characterizations of Three Major Cysteine Sensors of Keap1 in Stress Response","volume":"36","author":"Saito","year":"2016","journal-title":"Mol. Cell. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fonc.2017.00085","article-title":"The KEAP1NRF2 system in cancer","volume":"7","author":"Taguchi","year":"2017","journal-title":"Front. Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"11624","DOI":"10.1038\/ncomms11624","article-title":"Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription","volume":"7","author":"Kobayashi","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"967","DOI":"10.3109\/10715762.2014.948536","article-title":"Special issue on \u201cOxidative stress and mitochondrial alterations in aging and disease\u201d","volume":"48","author":"Chiu","year":"2014","journal-title":"Free Radic. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1093\/carcin\/bgp012","article-title":"15-Deoxy-Delta12,14-prostaglandin J2 upregulates the expression of heme oxygenase-1 and subsequently matrix metalloproteinase-1 in human breast cancer cells: Possible roles of iron and ROS","volume":"30","author":"Kim","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1089\/ars.2017.7358","article-title":"An Overview of the Advantages of KEAP1-NRF2 System Activation During Inflammatory Disease Treatment","volume":"29","author":"Suzuki","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1182\/blood-2010-05-285817","article-title":"Nrf2 and selenoproteins are essential for maintaining oxidative homeostasis in erythrocytes and protecting against hemolytic anemia","volume":"117","author":"Kawatani","year":"2011","journal-title":"Blood"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"9722","DOI":"10.1073\/pnas.1221743110","article-title":"Pirin is an iron-dependent redox regulator of NF-\u03baB","volume":"110","author":"Liu","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/S0891-5849(97)00016-6","article-title":"Iron homeostasis, oxidative stress, and DNA damage","volume":"23","author":"Meneghini","year":"1997","journal-title":"Free Radic. Biol. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.freeradbiomed.2013.06.020","article-title":"Bidirectional regulation of NF-\u03baB by reactive oxygen species: A role of unfolded protein response","volume":"65","author":"Nakajima","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6960","DOI":"10.1074\/jbc.R111.329847","article-title":"Nitrogen monoxide (NO) storage and transport by dinitrosyl-dithiol-iron complexes: Long-lived NO that is trafficked by interacting proteins","volume":"287","author":"Kalinowski","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.bbagen.2007.12.009","article-title":"The nitric oxide-iron interplay in mammalian cells: Transport and storage of dinitrosyl iron complexes","volume":"1780","author":"Richardson","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5146","DOI":"10.1073\/pnas.97.10.5146","article-title":"Direct nitric oxide signal transduction via nitrosylation of iron-sulfur centers in the SoxR transcription activator","volume":"97","author":"Ding","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1136\/bmj.2.2032.1595","article-title":"Clinical Remarks on Hypertrophic Cirrhosis of the Liver with Bronzing of the Skin: Haemochromatosis","volume":"2","author":"Osler","year":"1899","journal-title":"Br. Med. J."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/cphy.c120016","article-title":"Iron homeostasis in the liver","volume":"3","author":"Anderson","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1053\/gast.1996.v110.pm8613000","article-title":"Long-term survival in patients with hereditary hemochromatosis","volume":"110","author":"Niederau","year":"1996","journal-title":"Gastroenterology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/S0140-6736(15)01315-X","article-title":"Haemochromatosis","volume":"388","author":"Powell","year":"2016","journal-title":"Lancet"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1002\/hep.1840220417","article-title":"Portal hypertension and iron depletion in patients with genetic hemochromatosis","volume":"22","author":"Fracanzani","year":"1995","journal-title":"Hepatology"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"5305","DOI":"10.1210\/en.2004-0392","article-title":"Oxidative stress, beta-cell apoptosis, and decreased insulin secretory capacity in mouse models of hemochromatosis","volume":"145","author":"Cooksey","year":"2004","journal-title":"Endocrinology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.2337\/diabetes.51.4.1000","article-title":"Blood letting in high-ferritin type 2 diabetes: Effects on insulin sensitivity and beta-cell function","volume":"51","author":"Castro","year":"2002","journal-title":"Diabetes"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1093\/qjmed\/hcq170","article-title":"Venesection for non-alcoholic fatty liver disease unresponsive to lifestyle counselling--a propensity score-adjusted observational study","volume":"104","author":"Valenti","year":"2011","journal-title":"QJM"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.2337\/diacare.28.8.2061","article-title":"Prevalence of body iron excess in the metabolic syndrome","volume":"28","author":"Bozzini","year":"2005","journal-title":"Diabetes Care"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.cmet.2013.02.007","article-title":"Iron and diabetes risk","volume":"17","author":"Simcox","year":"2013","journal-title":"Cell Metab."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"e306","DOI":"10.1016\/j.lpm.2017.05.036","article-title":"Dysmetabolic iron overload syndrome (DIOS)","volume":"46","author":"Deugnier","year":"2017","journal-title":"Presse Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"62","DOI":"10.2337\/diacare.21.1.62","article-title":"Serum ferritin as a component of the insulin resistance syndrome","volume":"21","author":"Arroyo","year":"1998","journal-title":"Diabetes Care"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1309\/WWNE-KW2C-4KTW-PTJ5","article-title":"Histologic features of the liver in insulin resistance-associated iron overload. A study of 139 patients","volume":"116","author":"Turlin","year":"2001","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Marmur, J., Beshara, S., Eggertsen, G., Onel\u00f6v, L., Albiin, N., Danielsson, O., Hultcrantz, R., and St\u00e5l, P. (2018). Hepcidin levels correlate to liver iron content, but not steatohepatitis, in non-alcoholic fatty liver disease. BMC Gastroenterol., 18.","DOI":"10.1186\/s12876-018-0804-0"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/hep.24706","article-title":"NASH Clinical Research Network Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease","volume":"55","author":"Kowdley","year":"2012","journal-title":"Hepatology"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1053\/j.gastro.2009.11.013","article-title":"HFE genotype, parenchymal iron accumulation, and liver fibrosis in patients with nonalcoholic fatty liver disease","volume":"138","author":"Valenti","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.jhep.2010.09.037","article-title":"Risk of nonalcoholic steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease and low visceral adiposity","volume":"54","author":"Fracanzani","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"2448","DOI":"10.1111\/j.1572-0241.2001.04052.x","article-title":"Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis","volume":"96","author":"Fargion","year":"2001","journal-title":"Am. J. Gastroenterol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1111\/j.1478-3231.2011.02488.x","article-title":"Serum ferritin is a discriminant marker for both fibrosis and inflammation in histologically proven non-alcoholic fatty liver disease patients","volume":"31","author":"Manousou","year":"2011","journal-title":"Liver Int."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1002\/hep.27774","article-title":"Increased duodenal iron absorption through up-regulation of divalent metal transporter 1 from enhancement of iron regulatory protein 1 activity in patients with nonalcoholic steatohepatitis","volume":"62","author":"Hoki","year":"2015","journal-title":"Hepatology"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.jhep.2011.05.008","article-title":"Iron in fatty liver and in the metabolic syndrome: A promising therapeutic target","volume":"55","author":"Dongiovanni","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Beaton, M.D., Chakrabarti, S., Levstik, M., Speechley, M., Marotta, P., and Adams, P. (2013). Phase II clinical trial of phlebotomy for non-Alcoholic fatty liver disease. Aliment. Pharmacol. Ther.","DOI":"10.1111\/apt.12255"},{"key":"ref_127","unstructured":"Webb, M., Ching, H.L.I., Kava, J., Bynevelt, M., and Macquillan, G.C. (2015). The impact of phlebotomy in nonalcoholic fatty liver disease: A prospective, randomized, controlled trial. Hepatology."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"22974","DOI":"10.1074\/jbc.M602098200","article-title":"Alcohol metabolism-mediated oxidative stress down-regulates hepcidin transcription and leads to increased duodenal iron transporter expression","volume":"281","author":"Schafer","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1002\/hep.21895","article-title":"Iron-mediated regulation of liver hepcidin expression in rats and mice is abolished by alcohol","volume":"46","author":"Klein","year":"2007","journal-title":"Hepatology"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/j.1478-3231.2005.01004.x","article-title":"V Hepatic iron overload in alcoholic end-stage liver disease is associated with iron deposition in other organs in the absence of HFE-1 hemochromatosis","volume":"25","author":"Eng","year":"2005","journal-title":"Liver Int."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1097\/MEG.0b013e328355cfd0","article-title":"Liver hepcidin mRNA expression is inappropriately low in alcoholic patients compared with healthy controls","volume":"24","author":"Batista","year":"2012","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/S0168-8278(05)80530-6","article-title":"Iron increases ethanol toxicity in rat liver","volume":"17","author":"Hultcrantz","year":"1993","journal-title":"J. Hepatol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1172\/JCI118077","article-title":"Experimental liver cirrhosis induced by alcohol and iron","volume":"96","author":"Tsukamoto","year":"1995","journal-title":"J. Clin. Invest."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1053\/gast.2002.30992","article-title":"Excess alcohol greatly increases the prevalence of cirrhosis in hereditary hemochromatosis","volume":"122","author":"Fletcher","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0741-8329(03)00126-5","article-title":"Iron-induced oxidant stress in alcoholic liver fibrogenesis","volume":"30","author":"Pietrangelo","year":"2003","journal-title":"Alcohol"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1053\/jhep.2002.31782","article-title":"Risk factors of fibrosis in alcohol-induced liver disease","volume":"35","author":"Raynard","year":"2002","journal-title":"Hepatology"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1136\/gut.46.2.277","article-title":"Liver iron is predictive of death in alcoholic cirrhosis: A multivariate study of 229 consecutive patients with alcoholic and\/or hepatitis C virus cirrhosis: A prospective follow up study","volume":"46","author":"Christidis","year":"2000","journal-title":"Gut"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Ma, L., Zou, T., Yuan, Y., Lv, J., Dong, X., Yang, G., Zhu, Y., Luo, J., Zhang, Z., and Yang, J. (2014). Duodenal ferroportin is up-regulated in patients with chronic hepatitis C. PLoS One, 9.","DOI":"10.1371\/journal.pone.0110658"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.freeradbiomed.2006.11.001","article-title":"Hepatic oxidative DNA damage correlates with iron overload in chronic hepatitis C patients","volume":"42","author":"Fujita","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1053\/j.gastro.2011.01.053","article-title":"HALT-C Trial Group Iron levels in hepatocytes and portal tract cells predict progression and outcomes of patients with advanced chronic hepatitis C","volume":"140","author":"Lambrecht","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.jhep.2006.09.021","article-title":"Liver iron is a surrogate marker of severe fibrosis in chronic hepatitis C","volume":"46","author":"Guyader","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"10777","DOI":"10.1073\/pnas.1301764110","article-title":"Identification of transferrin receptor 1 as a hepatitis C virus entry factor","volume":"110","author":"Martin","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1086\/422261","article-title":"Iron regulates hepatitis C virus translation via stimulation of expression of translation initiation factor 3","volume":"190","author":"Theurl","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1016\/j.jhep.2016.02.011","article-title":"Entry of hepatitis B and hepatitis D virus into hepatocytes: Basic insights and clinical implications","volume":"64","author":"Li","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/hep.25666","article-title":"Pegylated interferon-\u03b1 induced hypoferremia is associated with the immediate response to treatment in hepatitis C","volume":"56","author":"Ryan","year":"2012","journal-title":"Hepatology"},{"key":"ref_146","first-page":"605","article-title":"Serum ferritin as a predictor of treatment outcome in patients with chronic hepatitis C","volume":"104","author":"Ferrara","year":"2009","journal-title":"Am. J. Gastroenterol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1002\/hep.24787","article-title":"Serum ferritin levels are associated with a distinct phenotype of chronic hepatitis C poorly responding to pegylated interferon-alpha and ribavirin therapy","volume":"55","author":"Lange","year":"2012","journal-title":"Hepatology"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1136\/gutjnl-2016-313369","article-title":"Drug-induced liver injury: Recent advances in diagnosis and risk assessment","volume":"66","author":"Andrade","year":"2017","journal-title":"Gut"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.jhep.2017.07.005","article-title":"Acetaminophen (APAP) hepatotoxicity-Isn\u2019t it time for APAP to go away?","volume":"67","author":"Lee","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.redox.2016.10.001","article-title":"Oxidative stress during acetaminophen hepatotoxicity: Sources, pathophysiological role and therapeutic potential","volume":"10","author":"Du","year":"2016","journal-title":"Redox Biol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1007\/s12253-015-9946-3","article-title":"Ferroptosis is Involved in Acetaminophen Induced Cell Death","volume":"21","author":"Jemnitz","year":"2015","journal-title":"Pathol. Oncol. Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"133","DOI":"10.5487\/TR.2016.32.2.133","article-title":"Effect of Thiol-reducing Agents and Antioxidants on Sulfasalazine-induced Hepatic Injury in Normotermic Recirculating Isolated Perfused Rat Liver","volume":"32","author":"Heidari","year":"2016","journal-title":"Toxicol. Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jceh.2012.12.001","article-title":"Hepatotoxicity Related to Anti-tuberculosis Drugs: Mechanisms and Management","volume":"3","author":"Ramappa","year":"2013","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1093\/toxsci\/kfs176","article-title":"Acute acetaminophen intoxication leads to hepatic iron loading by decreased hepcidin synthesis","volume":"129","author":"Laarakkers","year":"2012","journal-title":"Toxicol. Sci."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1053\/j.gastro.2007.10.038","article-title":"Liver Iron, HFE Gene Mutations, and Hepatocellular Carcinoma Occurrence in Patients With Cirrhosis","volume":"134","author":"Nahon","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S1542-3565(03)00132-0","article-title":"HFE C282Y heterozygosity in hepatocellular carcinoma: Evidence for an increased prevalence","volume":"1","author":"Hellerbrand","year":"2003","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Kowdley, K.V. (2004). Iron, hemochromatosis, and hepatocellular carcinoma. Gastroenterology.","DOI":"10.1016\/j.gastro.2004.09.019"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"992","DOI":"10.3389\/fphar.2017.00992","article-title":"The Role of Ferroptosis in Cancer Development and Treatment Response","volume":"8","author":"Lu","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1002\/ijc.28159","article-title":"Iron-dependent cell death of hepatocellular carcinoma cells exposed to sorafenib","volume":"133","author":"Louandre","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_160","first-page":"6417","article-title":"Sorafenib induces ferroptosis in human cancer cell lines originating from different solid tumors","volume":"34","author":"Lachaier","year":"2014","journal-title":"Anticancer Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.canlet.2014.11.014","article-title":"The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells","volume":"356","author":"Louandre","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1007\/s00432-018-2681-x","article-title":"Survival analysis and pathological features of advanced non-small cell lung cancer with miliary pulmonary metastases in patients harboring epidermal growth factor receptor mutations","volume":"144","author":"Okuma","year":"2018","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/hep.28251","article-title":"Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells","volume":"63","author":"Sun","year":"2016","journal-title":"Hepatology"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Craven, C.M., Alexander, J., Eldridge, M., Kushner, J.P., Bernstein, S., and Kaplan, J. (1987). Tissue distribution and clearance kinetics of non-transferrin-bound iron in the hypotransferrinemic mouse: A rodent model for hemochromatosis. Proc. Natl. Acad. Sci. USA.","DOI":"10.1073\/pnas.84.10.3457"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/j.1365-2141.1994.tb03267.x","article-title":"Intestinal iron absorption studies in mouse models of iron-overload","volume":"86","author":"Raja","year":"1994","journal-title":"Br. J. Haematol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"176","DOI":"10.3389\/fphar.2014.00176","article-title":"The IRP\/IRE system in vivo: Insights from mouse models","volume":"5","author":"Wilkinson","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Fleming, R.E., Feng, Q., and Britton, R.S. (2011). Knockout Mouse Models of Iron Homeostasis. Annu. Rev. Nutr.","DOI":"10.1146\/annurev-nutr-072610-145117"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1017\/S0007114510005507","article-title":"Iron absorption in hepcidin1 knockout mice","volume":"105","author":"Masaratana","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.jhep.2014.04.034","article-title":"Hepcidin knockout mice fed with iron-rich diet develop chronic liver injury and liver fibrosis due to lysosomal iron overload","volume":"61","author":"Lunova","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"577","DOI":"10.3109\/00365521.2013.777468","article-title":"Hepatic encephalopathy is related to anemia and fat-free mass depletion in liver transplant candidates with cirrhosis","volume":"48","author":"Kalaitzakis","year":"2013","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1097\/MEG.0b013e3283319975","article-title":"Quality of life in cirrhosis is related to potentially treatable factors","volume":"22","author":"Les","year":"2010","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.cgh.2009.02.021","article-title":"Incidence, Prevalence, and Clinical Significance of Abnormal Hematologic Indices in Compensated Cirrhosis","volume":"7","author":"Qamar","year":"2009","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1023\/A:1018861415259","article-title":"Anemia worsens hyperdynamic circulation of patients with cirrhosis and portal hypertension","volume":"42","author":"Cirera","year":"1997","journal-title":"Dig. Dis. Sci."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41419-018-0506-0","article-title":"Ferroptosis-inducing agents compromise in vitro human islet viability and function article","volume":"9","author":"Bruni","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.chembiol.2019.01.008","article-title":"Imidazole Ketone Erastin Induces Ferroptosis and Slows Tumor Growth in a Mouse Lymphoma Model","volume":"26","author":"Zhang","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"ref_176","first-page":"1","article-title":"The ferroptosis inducer erastin irreversibly inhibits system xc- and synergizes with cisplatin to increase cisplatin\u2019s cytotoxicity in cancer cells","volume":"8","author":"Sato","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.3389\/fphar.2018.01371","article-title":"RSL3 drives ferroptosis through GPX4 inactivation and ros production in colorectal cancer","volume":"9","author":"Sui","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_178","first-page":"611","article-title":"Inactivation of the glutathione peroxidase GPx4 by the ferroptosis-inducing molecule RSL3 requires the adaptor protein 14-3-3\u03b5","volume":"594","author":"Bordin","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1002\/jcp.21366","article-title":"The xc- cystine\/glutamate antiporter: A potential target for therapy of cancer and other diseases","volume":"215","author":"Lo","year":"2008","journal-title":"J. Cell. Physiol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1038\/sj.leu.2402238","article-title":"Sulfasalazine, a potent suppressor of lymphoma growth by inhibition of the x-c cystine transporter: A new action for an old drug","volume":"15","author":"Gout","year":"2001","journal-title":"Leukemia"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"101328","DOI":"10.1016\/j.redox.2019.101328","article-title":"Insight into the mechanism of ferroptosis inhibition by ferrostatin-1","volume":"28","author":"Miotto","year":"2020","journal-title":"Redox Biol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1248\/bpb.b15-00048","article-title":"The 5-Lipoxygenase Inhibitor Zileuton Confers Neuroprotection against Glutamate Oxidative Damage by Inhibiting Ferroptosis","volume":"38","author":"Liu","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Kajarabille, N., and Latunde-Dada, G.O. (2019). Latunde-Dada Programmed Cell-Death by Ferroptosis: Antioxidants as Mitigators. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194968"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nchembio.2238","article-title":"Oxidized Arachidonic\/Adrenic Phosphatidylethanolamines Navigate Cells to Ferroptosis","volume":"13","author":"Kagan","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bbagen.2004.08.006","article-title":"Reevaluating the role of 1,10-phenanthroline in oxidative reactions involving ferrous ions and DNA damage","volume":"1675","author":"Silva","year":"2004","journal-title":"Biochim. Biophys. Acta - Gen. Subj."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.2174\/1568026616666161003143333","article-title":"The Antibacterial Activity of Metal Complexes Containing 1,10- phenanthroline: Potential as Alternative Therapeutics in the Era of Antibiotic Resistance","volume":"17","author":"Viganor","year":"2016","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"4073","DOI":"10.2147\/DDDT.S117080","article-title":"Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with nontransfusion-dependent thalassemia syndromes","volume":"10","author":"Taher","year":"2016","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1080\/13543784.2019.1631284","article-title":"Prospects for the introduction of targeted antioxidant drugs for the prevention and treatment of diseases related to free radical pathology","volume":"28","author":"Kontoghiorghes","year":"2019","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1056\/NEJMra1800219","article-title":"The role of deferiprone in iron chelation","volume":"379","author":"Hider","year":"2018","journal-title":"N. Engl. J. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/5\/1651\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:02:40Z","timestamp":1760173360000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/5\/1651"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,28]]},"references-count":189,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["ijms21051651"],"URL":"https:\/\/doi.org\/10.3390\/ijms21051651","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,28]]}}}