Participation of reactive oxygen metabolites in Clostridium difficile toxin A-induced enteritis in rats
Qiu, B.; Pothoulakis, C.; Castagliuolo, I.; Nikulasson, S.; LaMont, J.T.
American Journal of Physiology 276(2): G485-G490
1999
ISSN/ISBN: 0002-9513 PMID: 9950823 Document Number: 500075
Reactive oxygen metabolises (ROMs) contribute to the pathophysiology of intestinal inflammation. Our aim was to ascertain the involvement of ROMs in experimental ileitis in rats produced by toxin A of Clostridium difficile. Intraluminal toxin A caused a significant increase in hydroxyl radical and hydrogen peroxide production by ileal microsomes starting 1 h following toxin exposure and peaking at 2-3 h, and this was inhibited by pretreatment with DMSO, a ROM scavenger, or superoxide dismutase (SOD), which inactivates ROMs. In contrast, mucosal xanthine oxidase increased only slightly after toxin A exposure, and allopurinol, an inhibitor of xanthine oxidase, had no effect on toxin A-associated intestinal responses. Induction of neutropenia resulted in reduction of toxin-mediated free radical formation, fluid secretion, and permeability. The enterotoxic effects of C. difficile toxin A were associated with increased ROM release in ileal tissues and the ROM inhibitors DMSO and SOD inhibited these effects. This suggests that ROMs released during toxin A enteritis are released primarily from neutrophils invading the inflamed bowel segment. Reprinted by permission of the publisher.