Mitochondrial dysfunction, persistent oxidative damage, and catalase inhibition in immune cells of naïve and treated Crohn's disease

✍ Scribed by Belén Beltrán; Pilar Nos; Francisco Dasí; Marisa Iborra; Guillermo Bastida; Marcial Martínez; José-Enrique O'Connor; Guillermo Sáez; Inés Moret; Julio Ponce

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 424 KB
• Volume: 16
• Category: Article
• ISSN: 1078-0998
• DOI: 10.1002/ibd.21027

✦ Synopsis

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 (DWm) 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, DWm, 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. DWm 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 DWm 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.