{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:57:43Z","timestamp":1790661463044,"version":"4.1.0"},"reference-count":148,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T00:00:00Z","timestamp":1556582400000},"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>Iron is implicated in the pathogenesis of a number of human liver diseases. Hereditary hemochromatosis is the classical example of a liver disease caused by iron, but iron is commonly believed to contribute to the progression of other forms of chronic liver disease such as hepatitis C infection and nonalcoholic fatty liver disease. In this review, we present data from cell culture experiments, animal models, and clinical studies that address the hepatotoxicity of iron. These data demonstrate that iron overload is only weakly fibrogenic in animal models and rarely causes serious liver damage in humans, calling into question the concept that iron overload is an important cause of hepatotoxicity. In situations where iron is pathogenic, iron-induced liver damage may be potentiated by coexisting inflammation, with the resulting hepatocyte necrosis an important factor driving the fibrogenic response. Based on the foregoing evidence that iron is less hepatotoxic than is generally assumed, claims that assign a causal role to iron in liver injury in either animal models or human liver disease should be carefully evaluated.<\/jats:p>","DOI":"10.3390\/ijms20092132","type":"journal-article","created":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T02:07:19Z","timestamp":1556590039000},"page":"2132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Iron-Induced Liver Injury: A Critical Reappraisal"],"prefix":"10.3390","volume":"20","author":[{"given":"Steven A.","family":"Bloomer","sequence":"first","affiliation":[{"name":"Division of Science and Engineering, Penn State University, Abington College, Abington, PA 19001, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle E.","family":"Brown","sequence":"additional","affiliation":[{"name":"Iowa City Veterans Administration Medical Center, Iowa City, IA 52242, USA"},{"name":"Division of Gastroenterology-Hepatology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA"},{"name":"Program in Free Radical and Radiation Biology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/cld.350","article-title":"Role of iron in hepatocellular carcinoma","volume":"3","author":"Fargion","year":"2014","journal-title":"Clin. Liver Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Finianos, A., Mater, C.F., and Taher, A. (2018). Hepatocellular carcinoma in \u03b2-thalassemia patients: Review of the literature with molecular insight into liver carcinogenesis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19124070"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1159\/000343856","article-title":"Hepatic iron overload and hepatocellular carcinoma","volume":"3","author":"Kew","year":"2014","journal-title":"Liver Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1126\/science.1104742","article-title":"Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization","volume":"306","author":"Nemeth","year":"2004","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/labinvest.3700553","article-title":"Changes of gene expression of iron regulatory proteins during turpentine oil-induced acute-phase response in the rat","volume":"87","author":"Sheikh","year":"2007","journal-title":"Lab. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/labinvest.2012.52","article-title":"Ferroportin-1 is a \u2018nuclear\u2019-negative acute-phase protein in rat liver: A comparison with other iron-transport proteins","volume":"92","author":"Naz","year":"2012","journal-title":"Lab. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.freeradbiomed.2018.07.003","article-title":"Erythropoietic regulators of iron metabolism","volume":"133","author":"Ganz","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1016\/j.bbamcr.2012.01.014","article-title":"Hepcidin and iron homeostasis","volume":"1823","author":"Ganz","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_9","first-page":"152","article-title":"Functional role of DMT1 in transferrin-independent iron uptake by human hepatocyte and hepatocellular carcinoma cell, HLF","volume":"35","author":"Shindo","year":"2006","journal-title":"Hepatol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13612","DOI":"10.1073\/pnas.0606424103","article-title":"Zip14 (Slc39a14) mediates non-transferrin bound iron uptake into cells","volume":"103","author":"Liuzzi","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1172\/JCI112125","article-title":"Efficient clearance of non-transferrin-bound iron by rat liver: Implications for hepatic iron loading in iron overload states","volume":"76","author":"Brissot","year":"1985","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10909","DOI":"10.1016\/S0021-9258(18)67473-3","article-title":"Characterization of non-transferrin-bound iron clearance by rat liver","volume":"261","author":"Wright","year":"1986","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7347","DOI":"10.3748\/wjg.v23.i41.7347","article-title":"Reabsorption of iron into acutely damaged rat liver: A role for ferritins","volume":"23","author":"Malik","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1165\/ajrcmb.15.1.8679227","article-title":"Heme oxygenase-1: Function, regulation, and implications of a novel stress-inducible protein in oxidant-induced lung injury","volume":"15","author":"Choi","year":"1996","journal-title":"Am. J. Resp. Cell Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/S0891-5849(99)00002-7","article-title":"Iron and dioxygen chemistry is an important route to initiation of biological free radical oxidations: An electron paramagnetic resonance spin trapping study","volume":"26","author":"Qian","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/BF02576208","article-title":"Liver injury and generation of hydroxyl free radicals in experimental secondary hemochromatosis","volume":"193","author":"Figueiredo","year":"1993","journal-title":"Res. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1172\/JCI118205","article-title":"Iron supplementation generates hydroxyl radical in vivo. An ESR spin-trapping investigation","volume":"96","author":"Kadiiska","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/BF01972625","article-title":"Cell death and lipid peroxidation in isolated hepatocytes incubated in the presence of hydrogen peroxide and iron salts","volume":"66","author":"Latour","year":"1992","journal-title":"Arch. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/0003-9861(84)90010-9","article-title":"Mechanisms of the killing of cultured hepatocytes by hydrogen peroxide","volume":"228","author":"Rubin","year":"1984","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/0006-291X(85)90916-7","article-title":"Lysosomal origin of the ferric iron required for cell killing by hydrogen peroxide","volume":"133","author":"Starke","year":"1985","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1080\/15216540051080930","article-title":"Hydrogen peroxide. Ubiquitous in cell culture and in vivo?","volume":"50","author":"Halliwell","year":"2000","journal-title":"IUBMB Life"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.redox.2014.08.001","article-title":"Quantifying intracellular hydrogen peroxide perturbations in terms of concentration","volume":"2","author":"Huang","year":"2014","journal-title":"Redox Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1006\/bbrc.1995.1409","article-title":"The operation of Na+\/Ca2+ exchanger prevents intracellular Ca2+ overload and hepatocyte killing following iron-induced lipid peroxidation","volume":"208","author":"Carini","year":"1995","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3109\/10715768709069790","article-title":"Electron spin resonance studies on isolated hepatocytes treated with ferrous or ferric iron","volume":"3","author":"Poli","year":"1987","journal-title":"Free Radic. Res. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/toxsci\/kfq230","article-title":"Iron potentiates acetaminophen-induced oxidative stress and mitochondrial dysfunction in cultured mouse hepatocytes","volume":"118","author":"Moon","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1038\/labinvest.2009.92","article-title":"Phagocytosis of gadolinium chloride or zymosan induces simultaneous upregulation of hepcidin- and downregulation of hemojuvelin- and Fpn-1-gene expression in murine liver","volume":"89","author":"Moriconi","year":"2009","journal-title":"Lab. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"23707","DOI":"10.1074\/jbc.272.38.23707","article-title":"Nutrient deprivation of cultured rat hepatocytes increases the desferrioxamine-available iron pool and augments the sensitivity to hydrogen peroxide","volume":"272","author":"Roberg","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1002\/hep.22498","article-title":"Translocation of iron from lysosomes into mitochondria is a key event during oxidative stress-induced hepatocellular injury","volume":"48","author":"Uchiyama","year":"2008","journal-title":"Hepatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"R1165","DOI":"10.1152\/ajpregu.00719.2007","article-title":"Dysregulation of hepatic iron with aging: Implications for heat stress-induced oxidative liver injury","volume":"294","author":"Bloomer","year":"2008","journal-title":"Am. J. Physiol. Reg. Int. Comp. Physiol."},{"key":"ref_30","first-page":"1699","article-title":"Involvement of xanthine oxidase in oxidative stress and iron release during hyperthermic rat liver perfusion","volume":"52","author":"Powers","year":"1992","journal-title":"Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"967","DOI":"10.2353\/ajpath.2007.060441","article-title":"Erythrophagocytosis by liver macrophages (Kupffer cells) promotes oxidative stress, inflammation, and fibrosis in a rabbit model of steatohepatitis: Implications for the pathogenesis of human nonalcoholic steatohepatitis","volume":"170","author":"Otogawa","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/cbf.3238","article-title":"Strain- and time-dependent alterations in hepatic iron metabolism in a murine model of nonalcoholic steatohepatitis","volume":"34","author":"Bloomer","year":"2016","journal-title":"Cell Biochem. Funct."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"G251","DOI":"10.1152\/ajpgi.00137.2014","article-title":"A high-fat diet modulates iron metabolism but does not promote liver fibrosis in hemochromatotic Hjv\u2212\/\u2212 mice","volume":"308","author":"Padda","year":"2015","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0047-6374(98)00005-0","article-title":"Iron accumulation in aging: Modulation by dietary restriction","volume":"102","author":"Cook","year":"1998","journal-title":"Mech. Age. Dev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S0891-5849(99)00052-0","article-title":"Effect of age and caloric restriction on bleomycin-chelatable and nonheme iron in different tissues of C57BL\/6 mice","volume":"27","author":"Sohal","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1084\/jem.175.5.1181","article-title":"Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells","volume":"175","author":"Schreck","year":"1992","journal-title":"J. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"G719","DOI":"10.1152\/ajpgi.00108.2002","article-title":"Iron activates NF-\u03baB in Kupffer cells","volume":"283","author":"She","year":"2002","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lin, M., Rippe, R.A., Niemela, O., Brittenham, G., and Tsukamoto, H. (1997). Role of iron in NF-kappa B activation and cytokine gene expression by rat hepatic macrophages. Am. J. Physiol. Gastrointest. Liver Physiol., 272.","DOI":"10.1152\/ajpgi.1997.272.6.G1355"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.trsl.2006.03.002","article-title":"Chronic iron overload stimulates hepatocyte proliferation and cyclin D1 expression in rodent liver","volume":"148","author":"Brown","year":"2006","journal-title":"Transl. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/liv.12893","article-title":"Resveratrol mediates therapeutic hepatic effects in acquired and genetic murine models of iron-overload","volume":"36","author":"Das","year":"2016","journal-title":"Liver Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/labinvest.3700030","article-title":"Portal tract fibrogenesis in the liver","volume":"84","author":"Ramadori","year":"2004","journal-title":"Lab. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1016\/S0002-9440(10)64300-3","article-title":"Identification and characterization of the hepatic stellate cell transferrin receptor","volume":"162","author":"Bridle","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/S0006-2952(02)01257-1","article-title":"Effect of free iron on collagen synthesis, cell proliferation and MMP-2 expression in rat hepatic stellate cells","volume":"64","author":"Gardi","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.amjms.2017.08.012","article-title":"Iron enhances hepatic fibrogenesis and activates transforming growth factor-\u03b2 signaling in murine hepatic stellate cells","volume":"355","author":"Mehta","year":"2018","journal-title":"Am. J. Med. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s00535-007-2020-5","article-title":"The iron chelator deferoxamine causes activated hepatic stellate cells to become quiescent and to undergo apoptosis","volume":"42","author":"Jin","year":"2007","journal-title":"J. Gastroenterol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"G116","DOI":"10.1152\/ajpgi.1997.272.1.G116","article-title":"Effect of vitamin E supplementation on hepatic fibrogenesis in chronic dietary iron overload","volume":"272","author":"Brown","year":"1997","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/S0168-8278(97)80424-2","article-title":"Hepatic stellate cell activation in genetic haemochromatosis: Lobular distribution, effect of increasing hepatic iron and response to phlebotomy","volume":"26","author":"Ramm","year":"1997","journal-title":"J. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1002\/hep.510270622","article-title":"Hepatic stellate cells are not subjected to oxidant stress during iron-induced fibrogenesis in rodents","volume":"27","author":"Montosi","year":"1998","journal-title":"Hepatology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0168-8278(01)00222-7","article-title":"The labile iron pool of hepatocytes in chronic and acute iron overload and chelator-induced iron deprivation","volume":"36","author":"Zanninelli","year":"2002","journal-title":"J. Hepatol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1053\/jhep.2002.30362","article-title":"Stimulation and proliferation of primary rat hepatic stellate cells by cytochrome P450 2E1\u2013derived reactive oxygen species","volume":"35","author":"Nieto","year":"2002","journal-title":"Hepatology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1002\/hep.510270416","article-title":"(Latent) transforming growth factor \u03b2 in liver parenchymal cells, its injury-dependent release, and paracrine effects on rat hepatic stellate cells","volume":"27","author":"Roth","year":"1998","journal-title":"Hepatology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1002\/path.1875","article-title":"Iron-free neoplastic nodules and hepatocellular carcinoma without cirrhosis in Wistar rats fed a diet high in iron","volume":"208","author":"Asare","year":"2006","journal-title":"J. Pathol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1007\/BF01299922","article-title":"Experimental hepatic iron overload in the baboon: Results of a two-year study. Evolution of biological and morphologic hepatic parameters of iron overload","volume":"28","author":"Brissot","year":"1983","journal-title":"Dig. Dis. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1034\/j.1600-0676.2003.00832.x","article-title":"Effect of iron overload and dietary fat on indices of oxidative stress and hepatic fibrogenesis in rats","volume":"23","author":"Brown","year":"2003","journal-title":"Liver Int."},{"key":"ref_55","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_56","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/0168-8278(95)80222-3","article-title":"A long-term study of the interaction between iron and alcohol in an animal model of iron overload","volume":"22","author":"Olynyk","year":"1995","journal-title":"J. Hepatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1002\/hep.1840110513","article-title":"Liver gene expression during chronic dietary iron overload in rats","volume":"11","author":"Pietrangelo","year":"1990","journal-title":"Hepatology"},{"key":"ref_58","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_59","first-page":"521","article-title":"The effects of dietary iron on initiation and promotion in chemical hepatocarcinogenesis","volume":"21","author":"Hultcrantz","year":"1995","journal-title":"Hepatology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/labinvest.2013.121","article-title":"Excess iron modulates endoplasmic reticulum stress-associated pathways in a mouse model of alcohol and high-fat diet-induced liver injury","volume":"93","author":"Tan","year":"2013","journal-title":"Lab. Investig."},{"key":"ref_61","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. Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1172\/JCI110787","article-title":"Hepatic lipid peroxidation in vivo in rats with chronic iron overload","volume":"71","author":"Bacon","year":"1983","journal-title":"J. Clin. Investig."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/0006-2952(93)90074-7","article-title":"Metabolism of iron from (3,5,5-trimethylhexanoyl)ferrocene in rats. A dietary model for severe iron overload","volume":"45","author":"Nielsen","year":"1993","journal-title":"Biochem. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/S0168-8278(97)80362-5","article-title":"Studies on genotoxic effects of iron overload and alcohol in an animal model of hepatocarcinogenesis","volume":"27","author":"Olsson","year":"1997","journal-title":"J. Hepatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0378-4347(92)80219-G","article-title":"Trace quantitation of 4-hydroxy-2-nonenal in biological samples as its oxime-bis-tert.-butyldimethylsilyl derivative using 3-hydroxynonanal as an internal standard","volume":"578","author":"Kinter","year":"1992","journal-title":"J. Chromatogr."},{"key":"ref_66","first-page":"555","article-title":"Pathology of dietary carbonyl iron overload in rats","volume":"57","author":"Park","year":"1987","journal-title":"Lab. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/exmp.1999.2278","article-title":"Characterization of hepatic iron overload following dietary administration of dicyclopentadienyl iron (Ferrocene) to mice: Cellular, biochemical, and molecular aspects","volume":"68","author":"Valerio","year":"2000","journal-title":"Exp. Mol. Pathol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1016\/0016-5085(92)90331-R","article-title":"Liver pathology in genetic hemochromatosis: A review of 135 homozygous cases and their bioclinical correlations","volume":"102","author":"Deugnier","year":"1992","journal-title":"Gastroenterology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1007\/BF02890245","article-title":"Ultrastructural observations in the carbonyl iron-fed rat, an animal model for hemochromatosis","volume":"53","author":"Iancu","year":"1987","journal-title":"Virchows Arch. B Cell Pathol. Incl Mol. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1002\/hep.1840180318","article-title":"Effect of chronic iron overload on procollagen gene expression","volume":"18","author":"Roberts","year":"1993","journal-title":"Hepatology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1365-2141.1985.tb02997.x","article-title":"Pathogenesis of hepatic fibrosis in experimental iron overload","volume":"59","author":"Weintraub","year":"1985","journal-title":"Br. J. Haematol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2572","DOI":"10.1172\/JCI116495","article-title":"Genetic control of inflammatory gene induction and NF-kappa B-like transcription factor activation in response to an atherogenic diet in mice","volume":"91","author":"Liao","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/hep.1840130322","article-title":"Rapid induction of hepatic fibrosis in the gerbil after the parenteral administration of iron-dextran complex","volume":"13","author":"Carthew","year":"1991","journal-title":"Hepatology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1172\/JCI117861","article-title":"Molecular and cellular aspects of iron-induced hepatic cirrhosis in rodents","volume":"95","author":"Pietrangelo","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1046\/j.1365-2362.2002.01026.x","article-title":"Long-term sequelae of HFE deletion in C57BL\/6 x 129\/O1a mice, an animal model for hereditary haemochromatosis","volume":"32","author":"Lebeau","year":"2002","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1365-2613.2006.00491.x","article-title":"Comparative study between Hfe\u2212\/\u2212 and beta2m\u2212\/\u2212 mice: Progression with age of iron status and liver pathology","volume":"87","author":"Rodrigues","year":"2006","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/hep.25689","article-title":"Disruption of hemochromatosis protein and transferrin receptor 2 causes iron-induced liver injury in mice","volume":"56","author":"Delima","year":"2012","journal-title":"Hepatology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.redox.2016.11.013","article-title":"Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis","volume":"11","author":"Duarte","year":"2017","journal-title":"Redox Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1006\/taap.1995.1047","article-title":"Iron-induced lipid peroxidation in rat liver is accompanied by preferential induction of glutathione S-transferase 8-8 isozyme","volume":"131","author":"Khan","year":"1995","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.taap.2007.05.011","article-title":"Differential expression of stress-inducible proteins in chronic hepatic iron overload","volume":"223","author":"Brown","year":"2007","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.freeradbiomed.2006.10.039","article-title":"Increased hepatic telomerase activity in a rat model of iron overload: A role for altered thiol redox state?","volume":"42","author":"Brown","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_82","first-page":"128","article-title":"Dissociation between tissue iron concentrations and transferrin saturation among inbred mouse strains","volume":"126","author":"LeBoeuf","year":"1995","journal-title":"J. Lab. Clin. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"10663","DOI":"10.1073\/pnas.94.20.10663","article-title":"Strain-specific differences in mouse hepatic wound healing are mediated by divergent T helper cytokine responses","volume":"94","author":"Shi","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/hep.1840210430","article-title":"Iron overload facilitates hepatic fibrosis in the rat alcohol\/low-dose carbon tetrachloride model","volume":"21","author":"Mackinnon","year":"1995","journal-title":"Hepatology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1055\/s-2008-1040457","article-title":"Experimental models of hepatic fibrosis: A review","volume":"10","author":"Tsukamoto","year":"1990","journal-title":"Sem. Liver Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1136\/gut.12.5.363","article-title":"Experimental hepatic cirrhosis in dogs caused by chronic massive iron overload","volume":"12","author":"Lisboa","year":"1971","journal-title":"Gut"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/cbf.3110","article-title":"Tumour promotion versus tumour suppression in chronic hepatic iron overload","volume":"33","author":"Bloomer","year":"2015","journal-title":"Cell Biochem. Funct."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1093\/toxsci\/kfs193","article-title":"Elevated hepatic iron activates NF-E2\u2013related factor 2\u2013regulated pathway in a dietary iron overload mouse model","volume":"129","author":"Moon","year":"2012","journal-title":"Toxicol. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/S0168-8278(99)80201-3","article-title":"Dietary iron overload inhibits carbon tetrachloride-induced promotion in chemical hepatocarcinogenesis: Effects on cell proliferation, apoptosis, and antioxidation","volume":"30","author":"Wang","year":"1999","journal-title":"J. Hepatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1093\/toxsci\/kfr231","article-title":"3,5,5-Trimethyl-hexanoyl-ferrocene diet protects mice from moderate transient acetaminophen-induced hepatotoxicity","volume":"124","author":"Moon","year":"2011","journal-title":"Toxicol. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1111\/j.1478-3231.2006.01329.x","article-title":"Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease","volume":"26","author":"Kirsch","year":"2006","journal-title":"Liver Int."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1002\/hep.510290612","article-title":"Dietary iron overload and induced lipid peroxidation are associated with impaired plasma lipid transport and hepatic sterol metabolism in rats","volume":"29","author":"Brunet","year":"1999","journal-title":"Hepatology"},{"key":"ref_93","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_94","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/ng0896-399","article-title":"A novel MHC class 1-like gene is mutated in patients with hereditary hemochromatosis","volume":"13","author":"Feder","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1097\/00007890-199309000-00012","article-title":"An analysis of liver transplant experience from 37 transplant centers as reported to Medicare","volume":"56","author":"Kilpe","year":"1993","journal-title":"Transplantation"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"946","DOI":"10.7326\/0003-4819-129-11_Part_2-199812011-00005","article-title":"Hemochromatosis-associated mortality in the United States from 1979 to 1992: An analysis of Multiple-Cause Mortality Data","volume":"129","author":"Yang","year":"1998","journal-title":"Ann. Intern. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0140-6736(02)07447-0","article-title":"Penetrance of 845G\u2192A (C282Y) HFE hereditary haemochromatosis mutation in the USA","volume":"359","author":"Beutler","year":"2002","journal-title":"Lancet"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0140-6736(99)02195-9","article-title":"Haemochromatosis gene C282Y homozygotes in an elderly male population","volume":"354","author":"Willis","year":"1999","journal-title":"Lancet"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1046\/j.1365-2362.2002.01062.x","article-title":"No increase in mortality and morbidity among carriers of the C282Y mutation of the hereditary haemochromatosis gene in the oldest old: The Leiden 85-plus study","volume":"32","author":"Gussekloo","year":"2002","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1136\/bmj.327.7407.132","article-title":"Longevity and carrying the C282Y mutation for haemochromatosis on the HFE gene: Case control study of 492 French centenarians","volume":"327","author":"Coppin","year":"2003","journal-title":"BMJ"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1080\/003655201750422747","article-title":"Screening for hemochromatosis: High prevalence and low morbidity in an unselected population of 65,238 persons","volume":"36","author":"Asberg","year":"2001","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1007\/s00439-002-0824-1","article-title":"Hereditary haemochromatosis: Only 1% of adult HFE C282Y homozygotes in South Wales have a clinical diagnosis of iron overload","volume":"111","author":"McCune","year":"2002","journal-title":"Hum. Genet."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.cgh.2006.04.013","article-title":"Liver diseases in the hemochromatosis and iron overload screening study","volume":"4","author":"Adams","year":"2006","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1056\/NEJMoa073286","article-title":"Iron-overload-related disease in HFE hereditary hemochromatosis","volume":"358","author":"Allen","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1002\/hep.23786","article-title":"HFE C282Y homozygotes with serum ferritin concentrations below 1000 g\/L are at low risk of hemochromatosis","volume":"52","author":"Allen","year":"2010","journal-title":"Hepatology"},{"key":"ref_106","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_107","doi-asserted-by":"crossref","first-page":"4456","DOI":"10.1182\/blood-2007-11-122374","article-title":"Environmental and genetic modifiers of the progression to fibrosis and cirrhosis in hemochromatosis","volume":"111","author":"Wood","year":"2008","journal-title":"Blood"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/j.jhep.2005.01.023","article-title":"Association of myeloperoxidase promoter polymorphism with cirrhosis in patients with hereditary hemochromatosis","volume":"42","author":"Datz","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1001\/archinte.165.16.1835","article-title":"Prediction of progression to cirrhosis by glutathione S-transferase P1 polymorphism in subjects with hereditary hemochromatosis","volume":"165","author":"Stickel","year":"2005","journal-title":"Arch. Intern. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/hep4.1048","article-title":"Clinical burden of liver disease from hemochromatosis at an academic medical center","volume":"1","author":"Brown","year":"2017","journal-title":"Hepatol. Commun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/hep.21260","article-title":"Reversibility of hepatic fibrosis in treated genetic hemochromatosis: A study of 36 cases","volume":"44","author":"Falize","year":"2006","journal-title":"Hepatology"},{"key":"ref_112","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_113","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1053\/j.gastro.2011.06.065","article-title":"Improvement in liver pathology of patients with-thalassemia treated with deferasirox for at least 3 years","volume":"141","author":"Deugnier","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1016\/0016-5085(92)90339-Z","article-title":"Measurements of iron status in patients with chronic hepatitis","volume":"102","author":"Axiotis","year":"1992","journal-title":"Gastroenterology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0016-5085(98)70482-2","article-title":"Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis","volume":"114","author":"George","year":"1998","journal-title":"Gastroenterology"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/S0046-8177(96)90337-8","article-title":"Iron overload in patients with chronic hepatitis C: A clinicopathologic study","volume":"27","author":"Haque","year":"1996","journal-title":"Hum. Pathol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1053\/jhep.2002.33892","article-title":"HFE mutations, hepatic iron, and fibrosis: Ethnic-specific association of NASH with C282Y but not with fibrotic severity","volume":"36","author":"Chitturi","year":"2002","journal-title":"Hepatology"},{"key":"ref_118","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_119","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1002\/hep.510300604","article-title":"Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis","volume":"30","author":"Angulo","year":"1999","journal-title":"Hepatology"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1631\/jzus.2005.B1045","article-title":"Acute phase reaction and acute phase proteins","volume":"6","author":"Gruys","year":"2005","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1182\/blood.V99.10.3505","article-title":"Regulation of ferritin genes and protein","volume":"99","author":"Torti","year":"2002","journal-title":"Blood"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1365-2141.1977.tb00640.x","article-title":"Characterization of serum ferritin in iron overload: Possible identity to natural apoferritin","volume":"36","author":"Arosio","year":"1977","journal-title":"Br. J. Haematol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/hep.510280427","article-title":"Hepatic iron overload in patients with chronic viral hepatitis: Role of HFE mutations","volume":"28","author":"Piperno","year":"1998","journal-title":"Hepatology"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/S0168-8278(99)80308-0","article-title":"Liver iron accumulation in patients with chronic active hepatitis C: Prevalence and role of hemochromatosis gene mutations and relationship with hepatic histological lesions","volume":"31","author":"Hezode","year":"1999","journal-title":"J. Hepatol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0009-8981(00)00397-1","article-title":"Serum iron indices as a measure of iron deposits in chronic hepatitis C","volume":"304","author":"Fabris","year":"2001","journal-title":"Clin. Chim. Acta"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/S0168-8278(02)00305-7","article-title":"Iron and HFE or TfR1 mutations as comorbid factors for development and progression of chronic hepatitis C","volume":"37","author":"Bonkovsky","year":"2002","journal-title":"J. Hepatol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1182\/blood-2004-12-4855","article-title":"Hepcidin levels in humans are correlated with hepatic iron stores, hemoglobin levels, and hepatic function","volume":"106","author":"Detivaud","year":"2005","journal-title":"Blood"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1111\/j.1365-2893.2009.01244.x","article-title":"Serum hepcidin levels are related to the severity of liver histological lesions in chronic hepatitis C","volume":"17","author":"Tsochatzis","year":"2010","journal-title":"J. Viral Hepat."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/j.1600-0676.1996.tb00737.x","article-title":"Iron stores, response to alpha-interferon therapy, and effects of iron depletion in chronic hepatitis C","volume":"16","author":"Piperno","year":"1996","journal-title":"Liver"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0168-8278(98)80308-5","article-title":"A pilot randomized, controlled trial of the effect of iron depletion on long-term response to alpha-interferon in patients with chronic hepatitis C","volume":"28","author":"Fong","year":"1998","journal-title":"J. Hepatol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1053\/jhep.2000.8700","article-title":"Iron reduction as an adjuvant to interferon therapy in patients with chronic hepatitis C who have previously not responded to interferon: A multicenter, prospective, randomized, controlled trial","volume":"32","author":"Bonkovsky","year":"2000","journal-title":"Hepatology"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1002\/hep.510310325","article-title":"Iron reduction before and during interferon therapy of chronic hepatitis C: Results of a multicenter, randomized, controlled trial","volume":"31","author":"Fontana","year":"2000","journal-title":"Hepatology"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s10620-007-9945-7","article-title":"Phlebotomy improves therapeutic response to interferon in patients with chronic hepatitis C: A meta-analysis of six prospective randomized controlled trials","volume":"53","author":"Desai","year":"2008","journal-title":"Dig. Dis. Sci."},{"key":"ref_134","first-page":"8697","article-title":"Normalization of elevated hepatic 8-hydroxy-2-deoxyguanosine levels in chronic hepatitis C patients by phlebotomy and low iron diet","volume":"61","author":"Kato","year":"2001","journal-title":"Cancer Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1007\/s00535-007-2095-z","article-title":"Long-term phlebotomy with low-iron diet therapy lowers risk of development of hepatocellular carcinoma from chronic hepatitis C","volume":"42","author":"Kato","year":"2007","journal-title":"J. Gastroenterol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"E30","DOI":"10.1111\/hepr.12921","article-title":"Systematic review and meta-analysis to determine the impact of iron depletion in dysmetabolic iron overload syndrome and non-alcoholic fatty liver disease","volume":"48","author":"Murali","year":"2018","journal-title":"Hepatol. Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1136\/ard.42.1.89","article-title":"Effect of a specific iron chelating agent on animal models of inflammation","volume":"42","author":"Blake","year":"1983","journal-title":"Ann. Rheum Dis."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1136\/ard.46.4.327","article-title":"Effect of iron chelation on inflammatory joint disease","volume":"46","author":"Andrews","year":"1987","journal-title":"Ann. Rheum Dis."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1136\/ard.46.11.859","article-title":"Effect of nutritional iron deficiency on acute and chronic inflammation","volume":"46","author":"Andrews","year":"1987","journal-title":"Ann. Rheum Dis."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"R311","DOI":"10.1152\/ajpregu.00735.2007","article-title":"Attenuation of acute and chronic liver injury in rats by iron-deficient diet","volume":"294","author":"Otogawa","year":"2008","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.bcp.2015.09.001","article-title":"Antifibrotic mechanism of deferoxamine in concanavalin A induced-liver fibrosis: Impact on interferon therapy","volume":"98","author":"Darwish","year":"2015","journal-title":"Biochem. Pharmacol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3164\/jcbn.15-127","article-title":"Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib","volume":"58","author":"Yamamoto","year":"2016","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1073\/pnas.66.4.1244","article-title":"Iron: Its intracellular localization and possible role in cell division","volume":"66","author":"Robbins","year":"1970","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1039\/C7MT00116A","article-title":"The elemental role of iron in DNA synthesis and repair","volume":"9","author":"Puig","year":"2017","journal-title":"Metallomics"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/0008-8749(91)90336-A","article-title":"Role of iron in T cell activation: TH1 clones differ from TH2 clones in their sensitivity to inhibition of DNA synthesis caused by IgG MABs against the transferrin receptor and the iron chelator deferoxamine","volume":"134","author":"Thorson","year":"1991","journal-title":"Cell. Immun."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1079\/BJN19940094","article-title":"The effects of iron deficiency and iron overload on cell-mediated immunity in the mouse","volume":"72","author":"Omara","year":"1994","journal-title":"Br. J. Nutr."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"158","DOI":"10.4103\/0976-9668.127317","article-title":"Impact of iron deficiency anemia on cell-mediated and humoral immunity in children: A case-control study","volume":"5","author":"Das","year":"2014","journal-title":"J. Nat. Sci. Biol. Med."},{"key":"ref_148","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."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/9\/2132\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:48:07Z","timestamp":1760186887000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/9\/2132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,30]]},"references-count":148,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["ijms20092132"],"URL":"https:\/\/doi.org\/10.3390\/ijms20092132","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,30]]}}}