Changes in NADPH oxidase mRNA level can be detected in blood at inhaled corticosteroid treated asthmatic children

Life Sci. 2012 Nov 2;91(19-20):907-11. doi: 10.1016/j.lfs.2012.08.039. Epub 2012 Sep 13.

Abstract

Aim: Oxidative stress, observed in the asthmatic airways, is not localized only to the bronchial system. It would be a great advantage to monitor the oxidative stress markers from blood especially in childhood asthma following the inflammation. Our aim was to measure the levels of antioxidants and the oxidatively damaged biomolecules. We were also interested in the gene expression alterations of the free radical source gp91(phox) subunit (CYBB) of the NADPH oxidase system, and the antioxidant heme oxygenase-1 (HMOX-1) isoenzyme in the blood. Our findings were also examined in the context of medical treatment.

Main methods: Oxidative stress parameters via photometric methods, CYBB and HMOX-1 expressions via real-time PCR were measured in 58 asthmatic and 30 healthy children.

Key findings: Higher blood thiobarbituric acid reactive substances (TBARS) (p<0.03) and carbonylated protein (p<0.05) levels were found in the asthmatic children than in the controls. The relative expression of CYBB was significantly lower (p<0.05) in patients treated with a low daily dose of inhaled corticosteroid (ICS), than in asthmatics not receiving ICS therapy. Higher ICS doses alone or combined with long acting β2-receptor agonists did not influence the expression significantly. No similar tendency was found as regards to HMOX-1 expression.

Significance: Elevated levels of damaged lipid (TBARS) and protein (carbonylated) products corroborate the presence of oxidative stress in the blood during bronchial asthma and suggest the presence of chronic oxidative overload. Our findings also suggest that ICS treatment can influence the relative CYBB mRNA expression in circulating leukocytes in a dose dependent manner.

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenergic beta-2 Receptor Agonists / administration & dosage
  • Adrenergic beta-2 Receptor Agonists / pharmacology
  • Adrenergic beta-2 Receptor Agonists / therapeutic use
  • Asthma / drug therapy*
  • Case-Control Studies
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Gene Expression Regulation
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / pharmacology*
  • Glucocorticoids / therapeutic use
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Leukocytes / metabolism
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • NADPH Oxidase 2
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism*
  • Oxidative Stress*
  • Polymerase Chain Reaction
  • Protein Carbonylation
  • RNA, Messenger / metabolism
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Glucocorticoids
  • Membrane Glycoproteins
  • RNA, Messenger
  • Thiobarbituric Acid Reactive Substances
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • CYBB protein, human
  • NADPH Oxidase 2
  • NADPH Oxidases