{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:35:44Z","timestamp":1792787744817,"version":"4.5.0"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:00:00Z","timestamp":1491004800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2016,10,20]],"date-time":"2016-10-20T00:00:00Z","timestamp":1476921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National funds through Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia\/Minist\u00e9rio da Educa\u00e7\u00e3o e Ci\u00eancia","award":["PTDC\/SAU-FCF\/101177\/2008"],"award-info":[{"award-number":["PTDC\/SAU-FCF\/101177\/2008"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National funds through Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia\/Minist\u00e9rio da Educa\u00e7\u00e3o e Ci\u00eancia","award":["PTDC\/BIM-MET\/0739\/2012"],"award-info":[{"award-number":["PTDC\/BIM-MET\/0739\/2012"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National funds through Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia\/Minist\u00e9rio da Educa\u00e7\u00e3o e Ci\u00eancia","award":["SFRH\/BPD\/108207\/2015"],"award-info":[{"award-number":["SFRH\/BPD\/108207\/2015"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"crossref"}]},{"name":"COMPETE \u2013 Operational Competitiveness Programme","award":["FCOMP-01-0124-FEDER-011062"],"award-info":[{"award-number":["FCOMP-01-0124-FEDER-011062"]}],"id":[{"id":"https:\/\/ror.org\/022rdnn95","id-type":"ROR","asserted-by":"crossref"}]},{"name":"COMPETE \u2013 Operational Competitiveness Programme","award":["FCOMP-01-0124-FEDER-028447"],"award-info":[{"award-number":["FCOMP-01-0124-FEDER-028447"]}],"id":[{"id":"https:\/\/ror.org\/022rdnn95","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Norte Portugal Regional Operational Programme"},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Reitoria da Universidade do Porto\/Santander","award":["PP-IJUP2011-122"],"award-info":[{"award-number":["PP-IJUP2011-122"]}],"id":[{"id":"https:\/\/ror.org\/043pwc612","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Redox Biology"],"published-print":{"date-parts":[[2017,4]]},"DOI":"10.1016\/j.redox.2016.11.013","type":"journal-article","created":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T02:05:57Z","timestamp":1480557957000},"page":"157-169","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":44,"special_numbering":"C","title":["Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis"],"prefix":"10.1016","volume":"11","author":[{"given":"Tiago L.","family":"Duarte","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Caldas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana G.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Silva-Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreia","family":"Santos-Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jo\u00e3o","family":"Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gra\u00e7a","family":"Porto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Manuel","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.redox.2016.11.013_bib1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1053\/j.gastro.2010.06.013","article-title":"Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment","volume":"139","author":"Pietrangelo","year":"2010","journal-title":"Gastroenterology"},{"key":"10.1016\/j.redox.2016.11.013_bib2","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jhep.2016.01.037","article-title":"Mechanisms of iron hepatotoxicity","volume":"65","author":"Pietrangelo","year":"2016","journal-title":"J. Hepatol."},{"key":"10.1016\/j.redox.2016.11.013_bib3","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1586\/17474124.2.4.531","article-title":"Modifying factors of the HFE hemochromatosis phenotype","volume":"2","author":"Deugnier","year":"2008","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.redox.2016.11.013_bib4","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":"10.1016\/j.redox.2016.11.013_bib5","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1053\/j.gastro.2005.09.015","article-title":"Steatosis is a cofactor in liver injury in hemochromatosis","volume":"129","author":"Powell","year":"2005","journal-title":"Gastroenterology"},{"key":"10.1016\/j.redox.2016.11.013_bib6","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":"10.1016\/j.redox.2016.11.013_bib7","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1002\/hep.25720","article-title":"Clinical cofactors and hepatic fibrosis in hereditary hemochromatosis: the role of diabetes mellitus","volume":"56","author":"Wood","year":"2012","journal-title":"Hepatology"},{"key":"10.1016\/j.redox.2016.11.013_bib8","doi-asserted-by":"crossref","first-page":"13312","DOI":"10.1073\/pnas.96.23.13312","article-title":"Experimental hemochromatosis due to MHC class I HFE deficiency: immune status and iron metabolism","volume":"96","author":"Bahram","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.redox.2016.11.013_bib9","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\u00d7129\/O1a mice, an animal model for hereditary haemochromatosis","volume":"32","author":"Lebeau","year":"2002","journal-title":"Eur. J. Clin. Investig."},{"key":"10.1016\/j.redox.2016.11.013_bib10","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1111\/j.1365-2613.2006.00491.x","article-title":"Comparative study between Hfe-\/- and beta2m-\/- mice: progression with age of iron status and liver pathology","volume":"87","author":"Rodrigues","year":"2006","journal-title":"Int. J. Exp. Pathol."},{"key":"10.1016\/j.redox.2016.11.013_bib11","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","article-title":"Role of nrf2 in oxidative stress and toxicity","volume":"53","author":"Ma","year":"2013","journal-title":"Annu. Rev. Pharm. Toxicol."},{"key":"10.1016\/j.redox.2016.11.013_bib12","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1038\/labinvest.2008.75","article-title":"The Nrf2 transcription factor protects from toxin-induced liver injury and fibrosis","volume":"88","author":"Xu","year":"2008","journal-title":"Lab Investig."},{"key":"10.1016\/j.redox.2016.11.013_bib13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.taap.2010.01.013","article-title":"Nrf2 the rescue: effects of the antioxidative\/electrophilic response on the liver","volume":"244","author":"Klaassen","year":"2010","journal-title":"Toxicol. Appl. Pharm."},{"key":"10.1016\/j.redox.2016.11.013_bib14","doi-asserted-by":"crossref","first-page":"13079","DOI":"10.3748\/wjg.v20.i36.13079","article-title":"Role of Nrf2 in chronic liver disease","volume":"20","author":"Tang","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.redox.2016.11.013_bib15","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.jhep.2013.09.004","article-title":"Transcription factor NRF2 protects mice against dietary iron-induced liver injury by preventing hepatocytic cell death","volume":"60","author":"Silva-Gomes","year":"2014","journal-title":"J. Hepatol."},{"key":"10.1016\/j.redox.2016.11.013_bib16","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":"10.1016\/j.redox.2016.11.013_bib17","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":"10.1016\/j.redox.2016.11.013_bib18","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"10.1016\/j.redox.2016.11.013_bib19","doi-asserted-by":"crossref","first-page":"6066","DOI":"10.1021\/jf900576h","article-title":"Red wine protects against ethanol-induced oxidative stress in rat liver","volume":"57","author":"Assuncao","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.redox.2016.11.013_bib20","doi-asserted-by":"crossref","first-page":"7260","DOI":"10.3748\/wjg.v20.i23.7260","article-title":"Cellular and molecular mechanisms in the pathogenesis of liver fibrosis: an update","volume":"20","author":"Elpek","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.redox.2016.11.013_bib21","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1006\/bcmd.2002.0575","article-title":"Decreased liver hepcidin expression in the Hfe knockout mouse","volume":"29","author":"Ahmad","year":"2002","journal-title":"Blood Cells Mol. Dis."},{"key":"10.1016\/j.redox.2016.11.013_bib22","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.mad.2013.11.005","article-title":"Iron status in the elderly","volume":"136\u2013137","author":"Fairweather-Tait","year":"2014","journal-title":"Mech. Ageing Dev."},{"key":"10.1016\/j.redox.2016.11.013_bib23","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s00702-011-0588-7","article-title":"Ultrastructural aspects of iron storage, transport and metabolism","volume":"118","author":"Iancu","year":"2011","journal-title":"J. Neural Transm."},{"key":"10.1016\/j.redox.2016.11.013_bib24","series-title":"Lipid Peroxidation in Hepatic Fibrosis","author":"Shimizu","year":"2012"},{"key":"10.1016\/j.redox.2016.11.013_bib25","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1089\/ars.2014.6166","article-title":"Role of 4-hydroxynonenal-protein adducts in human diseases","volume":"22","author":"Barrera","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"10.1016\/j.redox.2016.11.013_bib26","first-page":"193","article-title":"Protein adducts of malondialdehyde and 4-hydroxynonenal in livers of iron loaded rats: quantitation and localization","volume":"173","author":"Khan","year":"2002","journal-title":"Toxicology"},{"key":"10.1016\/j.redox.2016.11.013_bib27","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S0022-2143(99)90022-7","article-title":"Hepatic lipid peroxidation in hereditary hemochromatosis and alcoholic liver injury","volume":"133","author":"Niemel\u00e4","year":"1999","journal-title":"J. Lab Clin. Med."},{"key":"10.1016\/j.redox.2016.11.013_bib28","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1002\/1873-3468.12301","article-title":"p62\/SQSTM1-Dr. Jekyll and Mr. Hyde that prevents oxidative stress but promotes liver cancer","volume":"590","author":"Taniguchi","year":"2016","journal-title":"FEBS Lett."},{"key":"10.1016\/j.redox.2016.11.013_bib29","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":"10.1016\/j.redox.2016.11.013_bib30","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/S1357-2725(02)00298-4","article-title":"Iron overload enhances the development of experimental liver cirrhosis in mice","volume":"35","author":"Arezzini","year":"2003","journal-title":"Int. J. Biochem Cell Biol."},{"key":"10.1016\/j.redox.2016.11.013_bib31","doi-asserted-by":"crossref","first-page":"e25138","DOI":"10.1371\/journal.pone.0025138","article-title":"Accelerated CCl4-induced liver fibrosis in Hjv-\/- mice, associated with an oxidative burst and precocious profibrogenic gene expression","volume":"6","author":"Sebastiani","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.redox.2016.11.013_bib32","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":"10.1016\/j.redox.2016.11.013_bib33","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1172\/JCI25049","article-title":"A mouse model of juvenile hemochromatosis","volume":"115","author":"Huang","year":"2005","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.redox.2016.11.013_bib34","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S0140-6736(03)12602-5","article-title":"Disrupted hepcidin regulation in HFE-associated haemochromatosis and the liver as a regulator of body iron homoeostasis","volume":"361","author":"Bridle","year":"2003","journal-title":"Lancet"},{"key":"10.1016\/j.redox.2016.11.013_bib35","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1007\/BF01308057","article-title":"A non-transferrin-bound serum iron in idiopathic hemochromatosis","volume":"25","author":"Batey","year":"1980","journal-title":"Dig. Dis. Sci."},{"key":"10.1016\/j.redox.2016.11.013_bib36","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1002\/hep.25538","article-title":"Probability of C282Y homozygosity decreases as liver transaminase activities increase in participants with hyperferritinemia in the hemochromatosis and iron overload screening study","volume":"55","author":"Adams","year":"2012","journal-title":"Hepatology"},{"key":"10.1016\/j.redox.2016.11.013_bib37","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/0270-9139(95)90052-7","article-title":"Kupffer cell iron overload induces intercellular adhesion molecule-1 expression on hepatocytes in genetic hemochromatosis","volume":"21","author":"Stal","year":"1995","journal-title":"Hepatology"},{"key":"10.1016\/j.redox.2016.11.013_bib38","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":"10.1016\/j.redox.2016.11.013_bib39","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":"10.1016\/j.redox.2016.11.013_bib40","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/hep.1840060106","article-title":"Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis","volume":"6","author":"Bassett","year":"1986","journal-title":"Hepatology"},{"key":"10.1016\/j.redox.2016.11.013_bib41","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/hep.1840110122","article-title":"The pathology of hepatic iron overload: a free radical \u2013 mediated process?","volume":"11","author":"Bacon","year":"1990","journal-title":"Hepatology"},{"key":"10.1016\/j.redox.2016.11.013_bib42","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/embor.2011.246","article-title":"Assurance of mitochondrial integrity and mammalian longevity by the p62-Keap1-Nrf2-Nqo1 cascade","volume":"13","author":"Kwon","year":"2012","journal-title":"EMBO Rep."},{"key":"10.1016\/j.redox.2016.11.013_bib43","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.bbrc.2013.05.051","article-title":"Mitochondrial targeting of mouse NQO1 and CYP1B1 proteins","volume":"435","author":"Dong","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.redox.2016.11.013_bib44","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev.pharmtox.45.120403.095857","article-title":"Glutathione transferases","volume":"45","author":"Hayes","year":"2005","journal-title":"Annu. Rev. Pharm. Toxicol."},{"key":"10.1016\/j.redox.2016.11.013_bib45","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":"10.1016\/j.redox.2016.11.013_bib46","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1016\/j.freeradbiomed.2005.02.015","article-title":"Glutathione conjugates of 4-hydroxy-2(E)-nonenal as biomarkers of hepatic oxidative stress-induced lipid peroxidation in rats","volume":"38","author":"V\u00f6lkel","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"10.1016\/j.redox.2016.11.013_bib47","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":"10.1016\/j.redox.2016.11.013_bib48","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/S0168-8278(03)00480-X","article-title":"4-Hydroxynonenal as a selective pro-fibrogenic stimulus for activated human hepatic stellate cells","volume":"40","author":"Zamara","year":"2004","journal-title":"J. Hepatol."}],"container-title":["Redox Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213231716302749?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2213231716302749?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T00:34:08Z","timestamp":1746837248000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2213231716302749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4]]},"references-count":48,"alternative-id":["S2213231716302749"],"URL":"https:\/\/doi.org\/10.1016\/j.redox.2016.11.013","relation":{},"ISSN":["2213-2317"],"issn-type":[{"value":"2213-2317","type":"print"}],"subject":[],"published":{"date-parts":[[2017,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis","name":"articletitle","label":"Article Title"},{"value":"Redox Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.redox.2016.11.013","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}