title: Mitochondrial dysfunction, persistent oxidative damage, and catalase inhibition in immune cells of naïve and treated Crohn's disease.
abstract: BACKGROUND
  Oxidative stress is considered a potential etiological factor for Crohn's disease (CD). We characterized the reactive oxygen species (ROS) generated in immune peripheral cells of CD patients, as well as their antioxidant enzyme status and the presence of oxidative damage. In addition, mitochondrial function (DeltaPsim) was analyzed to detect the possible origin of ROS.
  
  
  METHODS
  Cells were obtained from patients at the onset of disease, prior to any treatment. Experiments were repeated when patients were in clinical remission. A set of experiments was carried out in a group of CD patients in persistent morphological remission. Controls were healthy volunteers who were not receiving any treatment at the time. The generation of superoxide, hydrogen peroxide (H(2)O(2)) and nitric oxide, DeltaPsim, superoxide dismutase (SOD) and catalase (CAT) activities, and concentrations of malondyaldehyde (MDA) and 8-oxo-deoxyguanosine (8-oxo-dG) were measured.
  
  
  RESULTS
  SOD activity and H(2)O(2) production were significantly higher during active CD but returned to control levels in remission. DeltaPsim was inhibited during active CD and, although it returned to control levels, its recovery took longer than clinical remission. CAT activity was permanently inhibited during CD, independent of the disease activity. MDA and 8-oxo-dG were permanently elevated.
  
  
  CONCLUSIONS
  Oxidative stress during active CD depends on H(2)O(2) production. The inhibition of DeltaPsim suggests that this organelle is a source of ROS. CAT is permanently inhibited in CD, the biological significance of which is under study. The persistent oxidative damage detected may have implications for the evolution of the disease.
authors.affiliation: Department of Gastroenterology, Hospital Universitari La Fe, Valencia, Spain. beltran_belen@yahoo.es
authors.forename: Belén
authors.initials: B
authors.lastname: Beltrán
authors.forename: Pilar
authors.initials: P
authors.lastname: Nos
authors.forename: Francisco
authors.initials: F
authors.lastname: Dasí
authors.forename: Marisa
authors.initials: M
authors.lastname: Iborra
authors.forename: Guillermo
authors.initials: G
authors.lastname: Bastida
authors.forename: Marcial
authors.initials: M
authors.lastname: Martínez
authors.forename: José-Enrique
authors.initials: JE
authors.lastname: O'Connor
authors.forename: Guillermo
authors.initials: G
authors.lastname: Sáez
authors.forename: Inés
authors.initials: I
authors.lastname: Moret
authors.forename: Julio
authors.initials: J
authors.lastname: Ponce
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D016022:Case-Control Studies; D002374:Catalase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003424:Crohn Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D028361:Mitochondrial Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D009000:Monocytes / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016877:Oxidants; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D003849:Deoxyguanosine