Mitochondrial Dysfunction, Persistent Oxidative Damage, and Catalase Inhibition in Immune Cells of Naive and Treated Crohn's Disease
Mitochondrial Dysfunction, Persistent Oxidative Damage, and Catalase Inhibition in Immune Cells of Naive and Treated Crohn's Disease
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DOI:
10.1002/ibd.21027
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发表时间:
2010-01-01
影响因子:
4.9
通讯作者:
Ponce, Julio
中科院分区:
文献类型:
--
作者:
Beltran, Belen;Nos, Pilar;Ponce, Julio
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 (Delta psi m) was analyzed to detect the possible origin of ROS.Methods: Celts were obtained from patients at the onset of disease, prior to an), 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 health), volunteers who were not receiving any treatment at the time. The generation of superoxide, hydrogen peroxide (H2O2) and nitric oxide, Delta psi m, 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 H2O2 production were significantly higher during active CD but returned to control levels in remission. Delta psi m 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 H2O2 production. The inhibition of Delta psi m 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.