{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:22:04Z","timestamp":1790684524185,"version":"4.1.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2016,12,19]],"date-time":"2016-12-19T00:00:00Z","timestamp":1482105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2016,12,19]],"date-time":"2016-12-19T00:00:00Z","timestamp":1482105600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:p>Albumin is a potent scavenger of reactive oxygen species (ROS). However, modifications in albumin structure may reduce its antioxidant properties and modulate its immune\u2010regulatory functions. We examined alterations in circulating albumin in severe alcoholic hepatitis (SAH) patients and their contribution to neutrophil activation, intracellular stress, and alteration in associated molecular pathways. Albumin modifications and plasma oxidative stress were assessed in SAH patients (n = 90), alcoholic cirrhosis patients (n = 60), and healthy controls (n = 30) using liquid chromatography\/mass spectrometry and spectrophotometry. Activation and intracellular ROS were measured in healthy neutrophils after treatment with purified albumin from the study groups. Gene expression of SAH neutrophils was analyzed and compared to gene expression from healthy neutrophils after stimulation with purified albumin from SAH patient plasma. SAH\u2010albumin showed the highest albumin oxidative state (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.05) and prominent alteration as human nonmercaptalbumin 2 (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.05). Plasma oxidative stress (advanced oxidative protein product) was higher in SAH versus alcoholic cirrhosis patients and healthy controls (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.05). Neutrophil gelatinase\u2010associated lipocalin, myeloperoxidase, and intracellular ROS levels were highest in SAH\u2010albumin\u2010treated neutrophils (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.05). Genes associated with neutrophil activation, ROS production, intracellular antioxidation, and leukocyte migration plus genes for proinflammatory cytokines and various toll\u2010like receptors were overexpressed in SAH neutrophils compared to healthy neutrophils (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.05). Expression of the above\u2010mentioned genes in SAH\u2010albumin\u2010stimulated healthy neutrophils was comparable with SAH patient neutrophils, except for genes associated with apoptosis, endoplasmic reticulum stress, and autophagy (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.05). <jats:italic toggle=\"yes\">Conclusions<\/jats:italic>: In patients with SAH, there is a significant increase in albumin oxidation, and albumin acts as a pro\u2010oxidant; this promotes oxidative stress and inflammation in SAH patients through activation of neutrophils. (H<jats:sc>epatology<\/jats:sc> 2017;65:631\u2010646).<\/jats:p>","DOI":"10.1002\/hep.28897","type":"journal-article","created":{"date-parts":[[2016,10,24]],"date-time":"2016-10-24T14:46:51Z","timestamp":1477320411000},"page":"631-646","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":114,"title":["Hyperoxidized albumin modulates neutrophils to induce oxidative stress and inflammation in severe alcoholic hepatitis"],"prefix":"10.1097","volume":"65","author":[{"given":"Sukanta","family":"Das","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaswinder Singh","family":"Maras","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Shabir","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shvetank","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"David","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukriti","family":"Sukriti","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saggere Muralikrishna","family":"Shasthry","sequence":"additional","affiliation":[{"name":"Department of Hepatology,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakhi","family":"Maiwall","sequence":"additional","affiliation":[{"name":"Department of Hepatology,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirupama","family":"Trehanpati","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tej P.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biophysics,All India Institute of Medical Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv Kumar","family":"Sarin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine,Institute of Liver and Biliary Sciences,New Delhi,India"},{"name":"Department of Hepatology,Institute of Liver and Biliary Sciences,New Delhi,India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,12,19]]},"reference":[{"key":"hep28897-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1097\/MCG.0000000000000161","article-title":"Trends in alcoholic hepatitis\u2010related hospitalizations, financial burden, and mortality in the United States","volume":"49","year":"2015","journal-title":"J Clin Gastroenterol"},{"key":"hep28897-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"11893","DOI":"10.3748\/wjg.v21.i42.11893","article-title":"Advances in alcoholic liver disease: an update on alcoholic hepatitis","volume":"21","year":"2015","journal-title":"World J 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Granulocytes and mononuclear leukocytes on discontinuous density gradients of Ficoll\u2010Hypaque","volume":"5","year":"1974","journal-title":"J Immunol Methods"},{"key":"hep28897-bib-0030-20241017","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1080\/10715760600565752","article-title":"Oxidation of bovine serum albumin initiated by the Fenton reaction\u2014effect of EDTA, tert\u2010butylhydroperoxide and tetrahydrofuran","volume":"40","year":"2006","journal-title":"Free Radic Res"},{"key":"hep28897-bib-0031-20241017","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1046\/j.1523-1755.2001.00807.x","article-title":"Albumin is the major plasma protein target of oxidant stress in uremia","volume":"60","year":"2001","journal-title":"Kidney Int"},{"key":"hep28897-bib-0032-20241017","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ab.2010.01.006","article-title":"Enrichment of cysteinyl adducts of human serum 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