title: Glutathione imbalance in patients with X-linked adrenoleukodystrophy.
abstract: BACKGROUND
  X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder of X-linked inheritance caused by a mutation in the ABCD1 gene which determines an accumulation of long-chain fatty acids in plasma and tissues. Recent evidence shows that oxidative stress may be a hallmark in the pathogenesis of X-ALD and glutathione plays an important role in the defense against free radicals. In this study we have analyzed glutathione homeostasis in lymphocytes of 14 patients with X-ALD and evaluated the balance between oxidized and reduced forms of glutathione, in order to define the role of this crucial redox marker in this condition.
  
  
  METHODS
  Lymphocytes, plasma and erythrocytes were obtained from the whole blood of 14 subjects with X-ALD and in 30 healthy subjects. Total, reduced and protein-bound glutathione levels were measured in lymphocytes by HPLC analysis. Erythrocyte free glutathione and antioxidant enzyme activities, plasma thiols and carbonyl content were determined by spectrophotometric assays.
  
  
  RESULTS
  A significant decrease of total and reduced glutathione was found in lymphocytes of patients, associated to high levels of all oxidized glutathione forms. A decline of free glutathione was particularly significant in erythrocytes. The increased oxidative stress in X-ALD was additionally confirmed by the decrease of plasma thiols and the high level of carbonyls.
  
  
  CONCLUSIONS
  Our results strongly support a role for oxidative stress in the pathophysiology of X-ALD and strengthen the importance of the balance among glutathione forms as a hallmark and a potential biomarker of the disease.
authors.affiliation: Unit for Neuromuscular and Neurodegenerative Diseases, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Petrillo
authors.forename: Fiorella
authors.initials: F
authors.lastname: Piemonte
authors.forename: Anna
authors.initials: A
authors.lastname: Pastore
authors.forename: Giulia
authors.initials: G
authors.lastname: Tozzi
authors.forename: Chiara
authors.initials: C
authors.lastname: Aiello
authors.forename: Aurora
authors.initials: A
authors.lastname: Pujol
authors.forename: Marco
authors.initials: M
authors.lastname: Cappa
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005609:Free Radicals / Q000378:metabolism; D019803:Glutathione Disulfide / Q000097:blood*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018384:Oxidative Stress; D013438:Sulfhydryl Compounds / Q000097:blood
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters; D005609:Free Radicals; D013438:Sulfhydryl Compounds; D019803:Glutathione Disulfide
keywords: Glutathione; Oxidative stress; Redox markers; X-linked adrenoleukodystrophy (X-ALD)