title: A study of oxidative stress, cytokines and glutamate in Wilson disease and their asymptomatic siblings.
abstract: BACKGROUND
  Free copper in Wilson disease (WD) is toxic and may reduce antioxidant, increase oxidative stress marker and thereby cytokine release and excitotoxic injury, but there is paucity of studies in humans. We report oxidative stress markers, cytokines and glutamate in neurologic WD and correlate these with their clinical severity, laboratory findings and extent of Magnetic resonance imaging (MRI) changes.
  
  
  METHODS
  29 patients with neurologic WD and 9 asymptomatic WD siblings were included and their clinical, treatment history, disease severity, biochemical findings and MRI changes were noted. Glutathione (GSH), total antioxidant capacity (TAC) and malonodialdehyde (MDA) were measured by spectrophotometer, cytokines by cytokine bead array and glutamate by the fluorometer.
  
  
  RESULTS
  In WD patients, the glutathione (mean±SEM, 2.20±0.06 vs. 2.73±0.04mg/dl, P<0.001) and TAC (1.70±0.03 vs. 2.29±0.02 Trolox_Eq_mmol/l, P<0.001) were reduced, and MDA and glutamate (23.93±0.54 vs. 19.96±0.27μmol/l; P<0.001) were increased (4.7±0.11 vs. 3.03±0.52nmol/ml, P<0.001) compared to controls. The serum IL6 {median (IQRs), 9.42(10.92) vs. 5.2(5.34) pg/ml; P=0.001}, IL8 {12.37(10.92) vs. 5.63(5.52) pg/ml; P<0.001}, IL10 {8.33(8.3) vs. 2.05(1.37) pg/ml; P=0.001} and TNFα {6.14(8.95) vs. 3.61(3.58) pg/ml; P<0.001} were also increased in WD patients compared to controls. These changes were more marked in the neurologic WD compared to asymptomatic WD and in the untreated compared to treated patients. TAC correlated with duration of illness, serum free copper, 24hour urinary copper and serum ceruloplasmin, and glutamate with MDA, TNFα, ceruloplasmin and 24-hour urinary copper.
  
  
  CONCLUSIONS
  In WD patients, antioxidants are reduced and MDA, cytokines and glutamate are increased which are more marked in symptomatic neurologic WD than asymptomatic patients.
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate medical Sciences, Lucknow, India. Electronic address: jayanteek@yahoo.com.
authors.forename: Jayantee
authors.initials: J
authors.lastname: Kalita
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate medical Sciences, Lucknow, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate medical Sciences, Lucknow, India.
authors.forename: Usha K
authors.initials: UK
authors.lastname: Misra
authors.affiliation: Department of Neurology, Sanjay Gandhi Post Graduate medical Sciences, Lucknow, India.
authors.forename: Abhay
authors.initials: A
authors.lastname: Ranjan
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Hamidullah
authors.initials: H
authors.lastname: Khan
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Rituraj
authors.initials: R
authors.lastname: Konwar
mesh_terms: D000293:Adolescent; D000975:Antioxidants / Q000378:metabolism; D002648:Child; D003300:Copper / Q000378:metabolism; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006527:Hepatolenticular Degeneration / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D015227:Lipid Peroxidation / Q000276:immunology; D008297:Male; D018384:Oxidative Stress / Q000276:immunology*; D035781:Siblings; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D000975:Antioxidants; C508606:CXCL8 protein, human; D016207:Cytokines; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018698:Glutamic Acid; D003300:Copper; D005978:Glutathione
keywords: Copper; Cytokine; Glutamate; Glutathione; Lipid peroxidation; Wilson disease