Role of reactive oxygen metabolites in experimental colitis.

Abstract

Reactive oxygen metabolites are potent inflammatory mediators that may be involved in tissue injury in inflammatory bowel disease. To evaluate their role in inflammatory bowel disease, we investigated the effects oflowering the activities of reactive oxygen metabolites in experimental colitis induced by intracolonic administration of acetic acid in rats. Intracolonic administration of5% acetic acid caused severe inflammation (mean (SEM) inflammatory score was 24*3 (0.7) of a maximum score of 32). Acetic acid at 2-5% produced moderate inflammation (score= 17 (1.4) v 4-0 (0.5) in control rats). This lower dose was used for subsequent experiments. Specific superoxide anion scavenger methoxypolyethylene glycol:superoxide dismutase, and reactive oxygen metabolites scavenger, sulfasalazine, significantly decreased the severity of inflammation (s'cores: 8 (4.4) and 9-8 (2.2) respectively). The xanthine oxidase inhibitors, tungsten and pterin aldehyde, failed to improve inflammation but another xanthine oxidase inhibitor, aliopurinol, a compound with known superoxide anion scavenging effect, did limit the inflammation (10(2)). Inhibition ofhydroxyl radicalproduction by deferoxamine orlowering hydroxyl radical values by a scavenger, dimethyl sulfoxide, did not affect the severity of inflammation. These data suggest: (1) that reactive oxygen metabolites play an important role in experimental colitis, (2) that the xanthine oxidase pathway is not a major source of reactive oxygen metabolites in colitis, and (3) that tissue injury in experimental colitis is not caused by generation of hydroxyl radicals.

Protective effect of myricetin in dextran sulphate sodium-induced murine ulcerative colitis

“…Increased ROS levels in the intestinal epithelial cell membrane may lead to oxidative damage mediated by free radical attacks and lipid peroxidation, which may be an early critical event in the model of experimental IBD. Acute attacks of UC lead to an inflamed colonic mucosa, which contributes to an excess production of reactive oxygen metabolites by lipid peroxidation (18). Inflammatory tissue injury may further stimulate ROS production and reactive oxygen metabolites, thus forming a positive feedback loop and rendering the antioxidant system insufficient (19).…”

Current view of the immunopathogenesis in inflammatory bowel disease and its implications for therapy

“…A balance is maintained between oxidant and antioxidant systems under physiological conditions, but it is impaired in pathological success. Oxidant-mediated injury plays an important role in the pathophysiology of IBD [64] . It has been suggested that intestinal damage in IBD is related to increased free radical production and to impaired antioxidant defence systems [65] .…”

Large Intestine and Heat Shock Protein (HSP)

“…Oxidation stress in the large intestine is a cause and an aggravation factor not only of ulcerative colitis and Crohn disease but also of ischemic enteritis, infectious enteritis, and radiation colitis [22][23][24][25][26]. In the local inflammatory area of the large intestine, inflammatory infiltrative cells such as neutrophils produce various reactive oxygen species, which may damage the large intestinal mucosa.…”