title: Evidence that oxidative stress is increased in patients with X-linked adrenoleukodystrophy.
abstract: X-linked adrenoleukodystrophy (X-ALD) is a hereditary disorder of peroxisomal metabolism biochemically characterized by the accumulation of very long chain fatty acids (VLCFA), particularly hexacosanoic acid (C26:0) and tetracosanoic acid (C24:0) in different tissues and in biological fluids. The disease is clinically characterized by central and peripheral demyelination and adrenal insufficiency, which is closely related to the increased concentrations of these fatty acids. However, the mechanisms underlying the brain damage in X-ALD are poorly known. Considering that free radical generation is involved in various neurodegenerative disorders, like Parkinson disease, multiple sclerosis and Alzheimer's disease, in the present study we evaluated various oxidative stress parameters, namely chemiluminescence, thiobarbituric acid reactive species (TBA-RS), total radical-trapping antioxidant potential (TRAP), and total antioxidant reactivity (TAR) in plasma of X-ALD patients, as well as the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in erythrocytes and fibroblasts from these patients. It was verified a significant increase of plasma chemiluminescence and TBA-RS, reflecting induction of lipid peroxidation, as well as a decrease of plasma TAR, indicating a deficient capacity to rapidly handle an increase of reactive species. We also observed a significant increase of erythrocytes GPx activity and of catalase and SOD activities in fibroblasts from the patients studied. It is therefore proposed that oxidative stress may be involved in pathophysiology of X-ALD.
authors.affiliation: Department of Clinical Analysis, Pharmacy Faculty, UFRGS, Rua Ramiro Barcelos, 2350 CEP 90.035-003, Porto Alegre, RS, Brazil. crvargas@hcpa.ufrgs.br
authors.forename: C R
authors.initials: CR
authors.lastname: Vargas
authors.forename: M
authors.initials: M
authors.lastname: Wajner
authors.forename: L R
authors.initials: LR
authors.lastname: Sirtori
authors.forename: L
authors.initials: L
authors.lastname: Goulart
authors.forename: M
authors.initials: M
authors.lastname: Chiochetta
authors.forename: D
authors.initials: D
authors.lastname: Coelho
authors.forename: A
authors.initials: A
authors.lastname: Latini
authors.forename: S
authors.initials: S
authors.lastname: Llesuy
authors.forename: A
authors.initials: A
authors.lastname: Bello-Klein
authors.forename: R
authors.initials: R
authors.lastname: Giugliani
authors.forename: M
authors.initials: M
authors.lastname: Deon
authors.forename: C F
authors.initials: CF
authors.lastname: Mello
mesh_terms: D000326:Adrenoleukodystrophy / Q000097:blood / Q000503:physiopathology*; D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000097:blood; D002478:Cells, Cultured; D002648:Child; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D013482:Superoxide Dismutase / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase