We studied the involvement of oxidative stress in chronic idiopathic urticaria (CIU), assessing the activities of superoxide dismutase (SOD) and glutathione and the levels of malondialdeyde (MDA), a marker of lipid peroxidation, in samples taken from lesional skin (n = 16) and nonlesional skin (n = 11) of CIU patients. The activity of SOD and glutathione and the levels of MDA were markedly increased in lesional skin as compared with skin of healthy subjects, whereas no differences were detected between nonlesional skin of CIU patients and control samples. Immuno-dot blot assay revealed an up-regulation of Mn-SOD expression in lesional skin. These findings show that oxidative stress is crucially involved in CIU. The evidence of lipid peroxidation and compensatory increase of Mn-SOD and glutathione activities in lesional skin, in the absence of any alteration in uninvolved skin, suggests that oxidative stress is secondary to the development of inflammation.
The inhibitor protein IF1 is a basic protein of 84 residues which inhibits the ATPase activity of the mitochondrial FoF1-ATP synthase complex without having any effect on ATP synthesis. Results of cross-linking and limited proteolysis experiments are presented showing that in the intact FoF1 complex "in situ," in the inner membrane of bovine heart mitochondria, the central segment of IF1 (residues 42-58) binds to the alpha and beta subunits of F1 in a pH dependent process, and inhibits the ATPase activity. The C-terminal region of IF1 binds, simultaneously, to the OSCP subunit of Fo in a pH-independent process. This binding keeps IF1 anchored to the complex, both under inhibitory conditions, at acidic pH, and noninhibitory conditions at alkaline pH.
Background Recent findings suggest the involvement of oxidative stress in the pathogenesis of chronic idiopathic urticaria (CIU). It has been demonstrated that desloratadine has an antioxidant activity in vitro . We evaluated the effects of desloratadine on markers of oxidative stress in patients with CIU. Methods Blood samples were obtained from 10 patients with CIU before and after 4 weeks of treatment with desloratadine. Blood samples from 10 healthy volunteers were used as controls.In platelets from both patients and controls, radical oxygen species (ROS) production was measured using spectrofluorimetric detection of dichloro-fluorescein oxidation, and superoxide dismutase (SOD) activity was determined by means of the xanthine-xanthine oxidase system.
ResultsRadical oxygen species concentrations and SOD activity were significantly elevated in patients with CIU at baseline as compared with control subjects. Treatment with desloratadine caused a relevant reduction of ROS levels and SOD activity ( P < 0.005).
ConclusionsThese preliminary results suggest that desloratadine exerts antioxidant effects also in vivo .
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