title: Decreased glutathione and low catalase activity contribute to oxidative stress in children with α-1 antitrypsin deficiency.
abstract: BACKGROUND
  Recent investigations in animal models have revealed oxidative stress and oxidative damage in the pathogenesis of alpha-1 antitrypsin deficiency (AATD). However, no data are available on the oxidative stress status and antioxidant enzyme activity in these patients. This study was aimed to analyse the oxidative stress profile and enzymatic antioxidant defence mechanisms in children with AATD.
  
  
  METHODS
  Oxidative stress parameters and the activity of the main antioxidant enzymes were prospectively measured in serum of fifty-one children diagnosed with AATD and thirty-eight control individuals.
  
  
  RESULTS
  Oxidative stress was increased in the serum of children with intermediate- (MZ; SZ) and high-risk (ZZ) phenotypes for developing AATD-related emphysema and/or liver disease. When compared with the control group, intermediate- and high-risk groups showed significantly lower total glutathione and reduced glutathione levels, decreased catalase activity and increased glutathione peroxidase activity leading to an accumulation of hydrogen peroxide that would explain the significantly increased levels of oxidative stress biomarkers observed in these patients. No differences were observed between the control (MM) and the low-risk (MS; SS) groups. A gradation in oxidative stress parameters was observed when patients were compared among themselves, in that the expression of the Z allele produces a higher oxidative stress status in homozygous (ZZ) than in heterozygous (MZ; SZ) patients.
  
  
  CONCLUSIONS
  Increased oxidative stress, together with reduced antioxidant defence are involved in the pathophysiology of AATD at early stages, opening up a new rationale for the use of antioxidant therapies in the treatment of the disease.
authors.affiliation: Department of Paediatrics, Obstetrics and Gynecology, School of Medicine, University of Valencia, Valencia, Spain Paediatrics Pneumology Unit, Hospital Clínico Universitario Valencia, Valencia, Spain Fundación Investigación Hospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Escribano
authors.affiliation: Department of Paediatrics, Obstetrics and Gynecology, School of Medicine, University of Valencia, Valencia, Spain Paediatrics Pneumology Unit, Hospital Clínico Universitario Valencia, Valencia, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Amor
authors.affiliation: Fundación Investigación Hospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Pastor
authors.affiliation: Department of Paediatrics, Obstetrics and Gynecology, School of Medicine, University of Valencia, Valencia, Spain Paediatrics Pneumology Unit, Hospital Clínico Universitario Valencia, Valencia, Spain Fundación Investigación Hospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Castillo
authors.affiliation: Pulmonology Unit, Consorcio Hospital General Universitario de Valencia, Valencia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sanz
authors.affiliation: Department of Paediatrics, Obstetrics and Gynecology, School of Medicine, University of Valencia, Valencia, Spain Paediatrics Unit, Hospital Universitario Dr. Peset Valencia, Valencia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Codoñer-Franch
authors.affiliation: Fundación Investigación Hospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Dasí
mesh_terms: D002374:Catalase / Q000378:metabolism*; D002648:Child; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D010641:Phenotype; D019896:alpha 1-Antitrypsin Deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D002374:Catalase; D005978:Glutathione
keywords: COPD ÀÜ Mechanisms; Emphysema; Oxidative Stress; Rare lung diseases