Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021390 (inflammatory bowel disease)
 23,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Injury to the gastrointestinal tract by oxygen dependent processes is important in ischemia, inflammatory bowel disease, and necrotizing enterocolitis. The Caco-2 cell line is an important tool in assessing various gastrointestinal functions and offers a unique opportunity to assess gastrointestinal oxidant metabolism on a cellular level. However, some Caco-2 cell functions change with time after confluence. To determine if antioxidant enzyme activity changes during differentiation, Caco-2 cells were grown to confluence, and superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase activities and specific mRNA content were quantitated. With time after confluence the enzymes demonstrated a small, but statistically significant increase in activity. Neither superoxide dismutase nor glutathione peroxidase mRNA levels correlated with enzyme activity changes. Catalase mRNA levels increased as catalase activity increased. Thus, differentiated Caco-2 cells express superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase activities and the superoxide dismutase, glutathione peroxidase, and catalase genes. Superoxide dismutase activity and glutathione peroxidase activity do not correlate with mRNA levels, and suggest that regulation may be at a level other than transcription. The correlation between catalase activity and catalase mRNA suggests differentiation may occur at transcription. If Caco-2 cells are used to elucidate oxidative metabolism, changes in activities of antioxidant enzymes as a function of cell differentiation should be considered.
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PMID:Antioxidant enzymes in the differentiated Caco-2 cell line. 142 66

Recent studies have demonstrated that intracolonic administration of trinitrobenzenesulfonic acid (TNB) dissolved in ethanol produces chronic colitis in rats, and that this model shares many features of human inflammatory bowel disease (IBD), particularly Crohn's disease. We investigated the role of free radicals in the pathogenesis of this colitis model. In the early stage of this colitis, antioxidant enzymes (such as superoxide dismutase, glutathione peroxidase) and an antioxidant, alpha-tocopherol, were significantly decreased with the severity of colonic damage. Mn-SOD at a dose of 50000 U/kg attenuated this colitis when preadministered subcutaneously one hour before the induction of colitis. These results suggest that oxygen-derived free radicals may play an important role in this colitis.
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PMID:Possible role of free radicals in the chronic inflammation of the gut. 145 May 97

There is a growing body of experimental data to suggest that the chronically inflamed intestine and/or colon may be subjected to considerable oxidative stress. The most probable sources of these oxidants are the phagocytic leukocytes since these cells are known to be present in large numbers in the inflamed mucosa and are known to produce significant amounts of reactive oxygen species in response to certain inflammatory stimuli. Because the colonic mucosa contains relatively small amounts of antioxidant enzymes (e.g. SOD, catalase, GSH peroxidase) it is possible that the gut mucosa may be overwhelmed during times of active inflammation which could result in intestinal injury. If reactive oxygen species play an important role in mediating mucosal injury in IBD then it should be possible to attenuate this injury by the use of antioxidants. One such drug is the sulfasalazine metabolite 5-ASA. It may not be coincidence that this potent antiinflammatory metabolite is a potent antioxidant that possesses multiple mechanisms of action including nitrogen, carbon and oxygen-centered free radical scavenging properties as well as the ability to decompose HOCl and scavenge hemoprotein-associated oxidants. In addition 5-ASA has the additional property of being able to chelate iron and render it poorly redox active. The reason that 5-ASA is so effective in vivo may be due to this multitude of antioxidant properties. This would also suggest that other, more potent antioxidants may prove beneficial in the treatment of IBD.
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PMID:Role of neutrophil-derived oxidants in the pathogenesis of intestinal inflammation. 166 88

Oxygen derived radicals contribute to tissue injury in inflammatory bowel disease. We measured the content of superoxide dismutase and metallothionein (two endogenous copper and zinc containing proteins involved in radical scavenging) in intestinal resection specimens from 29 patients with Crohn's disease and 12 patients with ulcerative colitis and compared the concentrations with those obtained in the normal mucosa of a control group of 18 patients with colorectal cancer. The superoxide dismutase content was similar in control mucosa and non-inflamed mucosa from patients with inflammatory bowel disease (mean (SEM) 2.13 (0.10) and 2.24 (0.10) mg/g protein, respectively) but was decreased in inflamed mucosa (1.87 (0.08) mg/g protein, p less than 0.005 v non-inflamed mucosa). The metallothionein content was decreased in non-inflamed inflammatory bowel disease mucosa compared with control mucosa (0.23 (0.03) and 0.36 (0.04) mg/g protein, respectively, p less than 0.02) and a further decrease was found in inflamed mucosa (0.17 (0.02) mg/g protein, p less than 0.001 v control mucosa). No differences were found between Crohn's disease and ulcerative colitis and no significant effect of medication or tissue localisation was noted. These findings might indicate a decreased endogenous intestinal protection against oxygen derived radicals in inflammatory bowel disease which could contribute to the pathogenesis of the disease.
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PMID:Decrease in two intestinal copper/zinc containing proteins with antioxidant function in inflammatory bowel disease. 195 69

Reactive oxygen metabolites have been implicated as important mediators of inflammation-induced intestinal injury associated with ischemia (and reperfusion), radiation, and inflammatory bowel disease. Because the colonic mucosa may be subjected to significant oxidant stress during times of acute and chronic inflammation, knowledge of the oxidant defense mechanisms in the colon is of biologic and potential clinical importance. Therefore, the objective of this study was to quantify the specific activities of superoxide dismutase (SOD), catalase, and GSH peroxidase in the normal human colon. We found low, but significant, amounts of all three enzymes in the mucosa, submucosa, and muscularis/serosa of the human colon. However, the mucosal, levels of SOD (3.6 +/- 0.3 units/mg protein), catalase (11 +/- 3 units/mg), and GSH peroxidase (15.2 +/- 0.8 mU/mg) represented only 8%, 4%, and 40%, respectively, of those values determined for human liver. Colonic epithelial cells derived from mucosal biopsies exhibited significantly higher specific activities for SOD (12 +/- 0.5 units/mg) and catalase (26 +/- 6 units/mg) when compared to whole mucosa, suggesting most of the mucosal activity was associated with the epithelial cells and not the lamina propria. In a comparative study, we found that a human colonic carcinoma cell line (CaCo-2) contained significantly lower SOD (6 +/- 0.5 units/mg) and catalase (6 +/- 0.6 units/mg) activities when compared to colonic epithelial cells. Taken together, our data suggest that: (1) the colonic mucosa is relatively deficient in antioxidant enzymes when compared to liver, and (2) most of the protective enzyme activity is localized within the epithelium and not the mucosal interstitium.
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PMID:Oxidant defense mechanisms in the human colon. 209 May 86

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 of lowering the activities of reactive oxygen metabolites in experimental colitis induced by intracolonic administration of acetic acid in rats. Intracolonic administration of 5% 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 (scores: 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, allopurinol, a compound with known superoxide anion scavenging effect, did limit the inflammation (10(2)). Inhibition of hydroxyl radical production by deferoxamine or lowering 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.
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PMID:Role of reactive oxygen metabolites in experimental colitis. 186 49

The lesson learned from the studies on oxygen-derived free radicals and several well recognized metabolic and morphologic disturbances associated with IBD and intestinal ischaemia strongly suggests that oxyradicals can be an important mediators of colonic injury in UC. Instead of summarizing of what has been said, a schematic illustration of different pathogenetic factors which can way a vicious circle of destruction is proposed. Unfortunately, a new and specific therapy of UC is as yet not available, because the locus of primary lesion is poorly understood. It is, however, reasonable to search for a complex therapy which could break a chain of pathological processes at several subunits functioning in either positive or negative feed-back loops. In my belief, complementary treatment with free-radical scavengers is to be tested as a new and potentially efficacious modality. In this respect, preliminary encouraging results obtained with local administration of SOD encapsulated in liposomes deserve attention.
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PMID:The role of reactive oxygen metabolites in the pathogenesis of ulcerative colitis: a speculative synthesis. 248 39

We have examined the interactions of 5-aminosalicylic acid with nitric oxide (NO). Phenylephrine-precontracted rat aortic strips with intact endothelium were further contracted by 5-aminosalicylic acid (50-200 microM) in a concentration-dependent manner. Removal of endothelium, inhibition of guanylate cyclase by methylene blue, inhibition of NO biosynthesis by NG-nitro-L-arginine as well as in inactivation of NO by oxyhemoglobin abolished the effect of 5-aminosalicylic acid. The antiaggregatory effects of 3-morpholinosydnonimine and rat peritoneal neutrophils, which are due to release of NO, were diminished in a concentration-dependent manner by 5-aminosalicylic acid (50-250 microM). In both experimental models the effects of 5-aminosalicylic acid were significantly reduced by superoxide dismutase in a concentration which alone exhibited no effect. Since NO might act as a cytotoxic and vasodilating mediator, our results suggest that inactivation of NO by 5-aminosalicylic acid could contribute to the therapeutic activity of the drug in inflammatory bowel disease.
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PMID:Interaction of 5-aminosalicylic acid with nitric oxide on rat aortic strips and human platelets. 749 69

During active inflammatory bowel disease (IBD) the respiratory burst of neutrophil granulocytes has been shown to be impaired using isolated circulating neutrophil granulocytes of patients with active disease. Using normal neutrophil granulocytes of healthy volunteers the present study examines the potential priming effect of sera of patients with active and quiescent IBD. The superoxide anion (O2-)-release of normal neutrophil granulocytes in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) has been investigated after incubation with sera of patients with active and inactive Crohn's disease and ulcerative colitis. O2(-)-release was measured using the superoxide dismutase inhibitable reduction of ferricytochrome c. The O2(-)-release of normal neutrophil granulocytes primed with sera of patients with inactive Crohn's disease (607.1 +/- 218.2 nmol/60 min, n = 10, p = 0.001) or cultured with sera of patients with quiescent ulcerative colitis (497.4 +/- 94.9 nmol/60 min, n = 3, p = 0.005) was significantly enhanced when compared with sera of normal controls (319.8 +/- 86.5 nmol/60 min, n = 10). There was no significant difference between priming with sera of patients with quiescent or active Crohn's disease (481.0 +/- 113.0 nmol/60 min, n = 5). Normal neutrophil granulocytes primed with sera of patients with active ulcerative colitis produce significantly larger amounts of O2- (809.5 +/- 256.9 nmol/60 min, n = 4, p = 0.001) when compared with sera of normal controls. The study shows that sera of patients with quiescent IBD as well as sera of patients with active disease have the potential to prime normal neutrophil granulocytes for an enhanced O2(-)-release in response to FMLP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhanced superoxide anion release of normal neutrophil granulocytes primed with sera of patients with inactive inflammatory bowel disease. 766 25

Oxygen-derived free radicals may contribute to intestinal tissue damage in inflammatory bowel disease. The concentrations of metallothionein and superoxide dismutase, two copper and zinc containing proteins involved in the scavenging of free radicals; were previously found to be decreased in the intestinal mucosa of patients with this disorder. The plasma zinc concentration is often decreased also in these patients. Since zinc is reported to be an efficient inducer of metallothionein synthesis, and probably of superoxide dismutase, we evaluated the effect of oral zinc supplementation on metallothionein and superoxide dismutase levels in patients with inflammatory bowel disease. Fourteen patients with inactive to moderately active inflammatory bowel disease received oral zinc supplementation (300 mg zinc aspartate, equal to 60 mg elemental zinc per day) for 4 weeks in a placebo-controlled double-blind cross-over trial. The plasma zinc concentration of these patients was low at the start of the study (12.2 +/- 1.7 mumol/L, P < 0.05), when compared to that of 22 healthy controls (13.6 +/- 2.3 mumol/L), but increased (P < 0.05) towards the levels of controls during the supplementation period (13.3 +/- 2.5 mumol/L). The concentrations of metallothionein and superoxide dismutase in plasma and in erythrocytes did not change in relation to the supplementation. The metallothionein concentration in both inflamed and non-inflamed intestinal mucosa was slightly higher after zinc supplementation but the superoxide dismutase concentration in the tissue was not altered. The histological inflammation score of intestinal biopsies, plasma albumin levels, and the disease activity index of the patients did not change during the study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of oral zinc supplementation on metallothionein and superoxide dismutase concentrations in patients with inflammatory bowel disease. 782 5


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