title: Hyperoxidized albumin modulates neutrophils to induce oxidative stress and inflammation in severe alcoholic hepatitis.
abstract: Albumin is a potent scavenger of reactive oxygen species (ROS). However, modifications in albumin structure may reduce its antioxidant properties and modulate its immune-regulatory 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-albumin showed the highest albumin oxidative state (P < 0.05) and prominent alteration as human nonmercaptalbumin 2 (P < 0.05). Plasma oxidative stress (advanced oxidative protein product) was higher in SAH versus alcoholic cirrhosis patients and healthy controls (P < 0.05). Neutrophil gelatinase-associated lipocalin, myeloperoxidase, and intracellular ROS levels were highest in SAH-albumin-treated neutrophils (P < 0.05). Genes associated with neutrophil activation, ROS production, intracellular antioxidation, and leukocyte migration plus genes for proinflammatory cytokines and various toll-like receptors were overexpressed in SAH neutrophils compared to healthy neutrophils (P < 0.05). Expression of the above-mentioned genes in SAH-albumin-stimulated healthy neutrophils was comparable with SAH patient neutrophils, except for genes associated with apoptosis, endoplasmic reticulum stress, and autophagy (P < 0.05).
  
  
  
  In patients with SAH, there is a significant increase in albumin oxidation, and albumin acts as a pro-oxidant; this promotes oxidative stress and inflammation in SAH patients through activation of neutrophils. (Hepatology 2017;65:631-646).
authors: Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
authors: Sukanta
authors: S
authors: Das
authors: Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
authors: Jaswinder Singh
authors: JS
authors: Maras
authors: Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
authors: Md Shabir
authors: MS
authors: Hussain
authors: Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
authors: Shvetank
authors: S
authors: Sharma
authors: Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
authors: Paul
authors: P
authors: David
authors: Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
authors: Sukriti
authors: S
authors: Sukriti
authors: Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
authors: Saggere Muralikrishna
authors: SM
authors: Shasthry
authors: Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
authors: Rakhi
authors: R
authors: Maiwall
authors: Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
authors: Nirupama
authors: N
authors: Trehanpati
authors: Department of Biophysics, All India Institute of Medical Sciences, New Delhi, India.
authors: Tej P
authors: TP
authors: Singh
authors: Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.|Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
authors: Shiv Kumar
authors: SK
authors: Sarin
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid; D003430:Cross-Sectional Studies; D005260:Female; D006519:Hepatitis, Alcoholic / Q000097:blood* / Q000473:pathology*; D006801:Humans; D000071068:Lipocalin-2 / Q000378:metabolism; D008111:Liver Function Tests; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D018375:Neutrophil Activation; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000097:blood*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric
chemical_list: C489506:LCN2 protein, human; D000071068:Lipocalin-2; D017382:Reactive Oxygen Species