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Decreased glutathione and low catalase activity contribute to oxidative stress in children with α-1 antitrypsin deficiency
  1. Amparo Escribano1,2,3,
  2. Mónica Amor1,2,
  3. Sara Pastor3,4,
  4. Silvia Castillo1,2,3,
  5. Francisco Sanz5,
  6. Pilar Codoñer-Franch1,6,
  7. Francisco Dasí3,4
  1. 1Department of Paediatrics, Obstetrics and Gynecology, School of Medicine, University of Valencia, Valencia, Spain
  2. 2Paediatrics Pneumology Unit, Hospital Clínico Universitario Valencia, Valencia, Spain
  3. 3Fundación Investigación Hospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, Valencia, Spain
  4. 4Department of Physiology, School of Medicine, University of Valencia, Valencia, Spain
  5. 5Pulmonology Unit, Consorcio Hospital General Universitario de Valencia, Valencia, Spain
  6. 6Paediatrics Unit, Hospital Universitario Dr. Peset Valencia, Valencia, Spain
  1. Correspondence to Dr Francisco Dasí, Fundación Investigación Hospital Clínico Universitario de Valencia/Instituto de Investigación Sanitaria INCLIVA, c/ Menéndez y Pelayo, 4, Valencia 46010, Spain; Francisco.Dasi{at}uv.es

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.

  • COPD ÀÜ Mechanisms
  • Emphysema
  • Oxidative Stress
  • Rare lung diseases

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