title: Intermittent Hypoxia Contributes to the Lung Damage by Increased Oxidative Stress, Inflammation, and Disbalance in Protease/Antiprotease System.
abstract: Intermittent hypoxia as a surrogate of obstructive sleep apnea is associated with different cardiovascular complications. However, the effects of intermittent hypoxia on the lung tissue are less known. Therefore, the aim of our present study was to investigate if intermittent hypoxia may influence oxidative stress, inflammation, and protease/antiprotease system in the lung. Additionally, potential protective properties of anti-inflammatory and anti-oxidative drugs have been evaluated.
  
  
  
  32 mice were divided into four groups: (1) intermittent hypoxia, (2) intermittent hypoxia with infliximab, (3) intermittent hypoxia with L-glutathione, and (4) normoxia. After 4 weeks, lungs and blood were collected. Levels of reactive oxygen species in the lung were calculated by L-O12-enhanced chemiluminescence. CD68-positive lung macrophages were detected by immunofluorescence. Concentrations of elastase and desmosine in lung and of alpha-1-antitrypsin in blood were calculated by means of enzyme-linked immunosorbent assay.
  
  
  
  Compared to a control, intermittent hypoxia augmented the release of free oxygen radicals, expression of CD68+ macrophages, and concentration of elastase in the lung tissue. Despite increased blood levels of protective alpha-1-antitrypsin, concentrations of desmosine-degradation product of elastin were higher versus control. The application of anti-inflammatory infliximab und anti-oxidative L-glutathione prevented at least partly the above-observed hypoxia-associated changes.
  
  
  
  Intermittent hypoxia contributes to the lung damage by increased oxidative stress, inflammation, and disbalance in protease/antiprotease system. Infliximab and L-glutathione may prevent adverse hypoxia-induced lung alternations.
authors.affiliation: Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany. Izabela.Tuleta@ukb.uni-bonn.de.
authors.forename: I
authors.initials: I
authors.lastname: Tuleta
authors.affiliation: Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Stöckigt
authors.affiliation: Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors.forename: U R
authors.initials: UR
authors.lastname: Juergens
authors.affiliation: Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Pizarro
authors.affiliation: Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors.forename: J W
authors.initials: JW
authors.lastname: Schrickel
authors.affiliation: Institute of Pathology, University of Bonn, Bonn, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Nickenig
authors.affiliation: Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Skowasch
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D000975:Antioxidants / Q000627:therapeutic use; D003895:Desmosine / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000627:therapeutic use; D000860:Hypoxia / Q000150:complications / Q000378:metabolism*; D007249:Inflammation / Q000097:blood* / Q000209:etiology / Q000517:prevention & control; D000069285:Infliximab / Q000627:therapeutic use; D008168:Lung / Q000378:metabolism*; D008264:Macrophages / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D010196:Pancreatic Elastase / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000097:blood*; D000097382:CD68 Molecule
chemical_list: D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000975:Antioxidants; D003895:Desmosine; D005978:Glutathione; D000069285:Infliximab; D010196:Pancreatic Elastase; D017382:Reactive Oxygen Species; D000515:alpha 1-Antitrypsin; C081026:CD68 protein, mouse; D000097382:CD68 Molecule
keywords: Antiproteases; Inflammation; Intermittent hypoxia; Oxidative stress; Proteases