{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:28:31Z","timestamp":1791275311283,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,5,15]],"date-time":"2003-05-15T00:00:00Z","timestamp":1052956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2003,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Intestinal mucosal damage in the inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) involves reactive oxygen metabolites (ROMs). ROMs are neutralized by endogenous antioxidant enzymes in a carefully balanced two\u2010step pathway. Superoxide dismutases (SODs) convert superoxide anion to hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>), which is subsequently neutralized to water by catalase (CAT) or glutathione peroxidase (GPO). Remarkably changed expression levels of the three isoforms of SOD in paired non\u2010inflamed and inflamed mucosae from CD and UC patients have been previously reported in comparison to normal control mucosa. Most notable was the strong up\u2010regulation of Mn\u2010SOD in inflamed epithelium. It was hypothesized that in order to provide optimal protection against ROM\u2010mediated damage, these changes should be coordinately counterbalanced by an increased H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010neutralizing capacity. Therefore, the same tissue samples were used to assess the levels, activities, and\/or localization of the most prominent mucosal H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010related antioxidants CAT, GPO, glutathione (GSH), myeloperoxidase (MPO), and metallothionein (MT). Quantitative measurements showed that in both CD and UC patients, intestinal inflammation was associated with increased activities of CAT, GPO, and MPO, whereas the mucosal GSH content was unaffected and the concentration of MT was decreased. Despite this overall increase in mucosal H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010metabolizing enzyme capacity, immunohistochemical analysis revealed a differentially disturbed antioxidant balance in IBD epithelium and lamina propria. In the lamina propria, the risk of direct H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010mediated damage seemed to be restrained by the increasing numbers of CAT\u2010 and MPO\u2010positive monocytes\/macrophages and neutrophils that infiltrated the inflamed areas. On the other hand, MPO overexpression might increase the lamina propria levels of hypochlorous acid, a stable ROM with multiple pro\u2010inflammatory effects. In the epithelium, the number of cells that expressed CAT remained unchanged during inflammation and GPO was found in only a very low and constant number of epithelial cells. In addition, the inflamed epithelium displayed decreased expression of the hydroxyl radical (OH<jats:sup>\u2022<\/jats:sup>) scavenger MT. In view of the high epithelial SOD levels in inflamed IBD epithelium, it is speculated that the efficient removal of excess H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> is hampered in these cells, thereby increasing not only the risk of detrimental effects of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> directly, but also those of its extremely reactive derivatives such as OH<jats:sup>\u2022<\/jats:sup>. Taken together, the results suggest an imbalanced and inefficient endogenous antioxidant response in the intestinal mucosa of IBD patients, which may contribute to both the pathogenesis and the perpetuation of the inflammatory processes. Copyright \u00a9 2003 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.1408","type":"journal-article","created":{"date-parts":[[2003,8,27]],"date-time":"2003-08-27T09:52:04Z","timestamp":1061977924000},"page":"17-27","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":186,"title":["Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease"],"prefix":"10.1002","volume":"201","author":[{"given":"Laurens","family":"Kruidenier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ineke","family":"Kuiper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"van Duijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marij 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