Excessive production of reactive oxygen metabolites by inflamed colon: Analysis by chemiluminescence probe (original) (raw)
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Chemiluminescence assay of mucosal reactive oxygen metabolites in inflammatory bowel disease
Gastroenterology, 1992
Previous studies suggesting increased reactive oxygen metabolite (ROM) production in inflammatory bowel disease have been restricted to peripheral blood and isolated intestinal phagocytes. In the current study, chemiluminescence and the effect of various scavengers, enzymes, and enzyme inhibitors were used to show that ROMs account for the increased production of oxidants by colorectal mucosal biopsy specimens in inflammatory bowel disease. Luminol-amplified chemiluminescence was increased in active ulcerative colitis [macroscopic grade 1: 25 photonsmg-'-min-10m3 (median), 8-47
Chemiluminescence in inflammatory bowel disease patients: a parameter of inflammatory activity
Clinica Chimica Acta, 2001
. Background: Reactive oxygen species ROS are produced in excess in the inflamed mucosa and peripheral blood of patients with inflammatory bowel disease. These species have emerged as a common pathway of tissue injury in a wide variety of inflammatory and other disease processes. The present study was conducted to assess ROS production and to Ž . correlate this with parameters of inflammatory activity. Methods: In 25 patients with Crohn's disease CD , 20 patients with Ž . ulcerative colitis UC and 65 age-and sex-matched healthy volunteers ROS production was measured using the whole Ž . blood luminol enhanced chemiluminescence assay LECA . Disease activity was assessed using the Crohn's disease activity Ž . index and the Ulcerative Colitis Symptoms Score UCSS for CD and UC, respectively. Furthermore, the effect of various scavengers, enzymes and enzyme inhibitors on LECA was studied to assess the contribution of different ROS. Results: Ž LECA was significantly higher in CD and UC patients compared with healthy controls 7.1 " 4.7 and 9.8 " 6 vs. 3 Ž . . Ž . 5.2 " 2.8 = 10 counts per minute cpm , p -0.05 and -0.001 . In CD, relative LECA patientrcontrol was correlated Ž . Ž . with the Crohn's disease activity index and C-reactive protein CRP r s 0.54, p s 0.001 and r s 0.51, p s 0.01 . In UC, Ž . CRP but not LECA was correlated with the Ulcerative Colitis Symptoms Score C-reactive protein: r s 0.42, p s 0.01 . Addition of azide, superoxide dismutase, deferoxamine and dimethylthiourea resulted in a decrease of LECA values. Conclusion: Whole blood LECA is increased in patients with CD and UC. This parameter is correlated with disease activity in CD. The observed chemiluminescence is probably due to generation of superoxide and the hydroxyl radical. q
The role of reactive oxygen metabolites in ulcerative colitis
Inflammatory Bowel Diseases, 1997
Reactive oxygen metabolites (ROMs) contribute to tissue injury in inflammatory bowel disease. The aim of this study is to examine the role of ROMs in the tissue injury in ulcerative colitis (UC). The study group consisted of 27 patients with UC (14 active, 13 quiescent) and a control group of 10 patients with various anal diseases. We measured the content of malondialdehyde (MDA), superoxide dismutase (SOD), and myeloperoxidase (MPO) in colorectal biopsies. MDA was measured by the thiobarbituric acid assay. SOD and MPO were measured using the nitro blue tetrazolium and o-dianisidine Ulcerative colitis (UC) is a common disorder of unknown etiology. Although the pathogenesis of UC is un
Decreased Total Antioxidant Capacity in Plasma, but Not Tissue, in Experimental Colitis
Digestive Diseases and Sciences, 2009
The aim of the present work was to compare colonic mucosa and plasmatic oxidative stress measured concomitantly and with different degrees of injury in rats with colitis induced by trinitrobenzene sulfonic acid. Three groups were studied: control group, colitis group, and colitis exacerbated by diclofenac. Enzymatic markers of colon injury showed enhanced activity in both groups with colitis. The colitis group treated with diclofenac presented higher colonic damage score than the other groups. In both groups with colitis, higher values of tert butyl hydroperoxide-initiated-chemiluminescence and thiobarbituric acid-reactive substances in tissue and decreased total radical-trapping antioxidant potential (TRAP) levels in plasma were found. In conclusion, independently of the degree of colonic mucosa injury and inflammation, oxidative stress in tissue occurs as a consequence of pro-oxidants increase, and is not explained by a reduction of antioxidant defenses. In both conditions, TRAP determination decreases in plasma, but not in tissue.
Gut, 1996
Background-Reactive oxygen species may mediate tissue injury in inflammatory bowel disease. Aminosalicylates have antioxidant activity and the antioxidants, superoxide dismutase and allopurinol, are of reported benefit in inflammatory bowel disease. Aim-To develop a convenient technique for testing the antioxidant potential of standard and novel therapeutic agents for use in inflammatory bowel disease. Methods-Amplified chemiluminescence was used to measure reactive oxygen species production by colonic biopsy specimens from rats with acetic acid induced colitis and to assess the in vitro effect of conventional antioxidants, standard therapies and proposed novel therapies for inflammatory bowel disease. Results-The model was validated by demonstrating that the profile ofeffects on chemiluminescence of acetic acid induced colitis biopsy specimens given by conventional antioxidants (sodium azide, catalase, copper-zinc superoxide dismutase, dimethyl sulphoxide, N-acetylcysteine and ascorbate) and standard therapies (5-aminosalicylate and hydrocortisone) resembled that previously reported using biopsy specimens from ulcerative colitis. Human recombinant manganese superoxide dismutase did not alter chemilumnescence. Two novel compounds, LY231617 (10 mM) and amflutizole (20 mM), reduced chemiluminescence by 98% (n=5, p=0.009) and 88% (n=5, p=0.03), respectively. Conclusions-The similarity of the chemiluminescence responses of colonic biopsy specimens from acetic acid induced colitis and ulcerative colitis to a range of conventional antioxidants and standard treatments suggests that this model is a useful method for testing the antioxidant potential of new therapies for inflammatory bowel disease. The antioxidant actions of dimethyl sulphoxide, ascorbate, and the novel compounds, amflutizole and LY231617 in this model suggest that these agents merit further assessment in the treatment of inflammatory bowel disease.
Journal of Gastroenterology and Hepatology, 1995
Oxygenderived free radicals have been implicated in the pathogenesis of ulcerative colitis. Mammalian tissues contain antioxidant systems that offer protection from the damaging effect of these active species. In the present study, the activity of the antioxidant enzymes catalase, glutathione peroxidase, glutathione transferase and glutathione reductase were measured in rectal biopsies from patients with ulcerative colitis and compared with that obtained from normal subjects. A significant decrease in the activity of glutathione transferase was observed in ulcerative colitis (48.32 f 6.73 unitslmg protein, mean f s.e.) compared to normal (68.20 f 6.83; P = 0.015). TheR was no difference in the activity of other antioxidant enzymes between controls and ulcerative colitis. Myeloperoxidase, a marker for neutrophil infiitration, was considerably increased in ulcerative colitis while malonaldehyd& the end product of lipid peroxidation, was not increased. The reduced activity of glutathione transferase in ulcerative colitis may be an additional factor in the pathogenesis of mucosal damage in this disease.
Redox report : communications in free radical research, 2017
To improve understanding of the preclinical stage of colonic inflammation by exploring the existence of a link between early inflammatory changes in the colonic mucosa and the systemic redox balance. Clinical characteristics, a fasting blood draw, and mucosal biopsies from the right, left, and sigmoid-rectum colonic tracts collected from 28 healthy individuals (14/14 males/females) who underwent colonoscopy. Myeloperoxidase (MPO) positive cells infiltrating colonic mucosa specimens were assessed by immunohistochemistry, and patients divided into high or low MPO expressing cells/optical field groups (MPO(high) or MPO(low), respectively).The systemic oxidative balance has been studied through derived-Reactive Oxygen Metabolites (d-ROMs), Biological Antioxidant Potential (BAP), and Lipoperoxide-cholesterol Oxidizing (LP-CHOLOX) tests on serum. MPO(high) patients demonstrated an increased systemic oxidative stress compared to MPO(low) individuals (P = 0.035), especially when MPO is refe...
The effect of antioxidant therapy on colonic inflammation in the rat
Research in Experimental Medicine, 1999
Under normal physiological conditions, chemical and antioxidant defenses protect tissues from the damaging effects of reactive oxygen metabolites (ROM). It has been proposed that ROMs are involved in the development of tissue injury in many inflammatory diseases and also in patients with colitis. In the present study we aimed to investigate the effects of antioxidant therapy on the extent of colonic inflammation and ROM levels in the injured tissues in a trinitrobenzene sulfonic acid-induced colitis model in the rat. Sprague-Dawley rats were pretreated with the antioxidants superoxide dismutase (30,000 U/kg s.c.) or catalase (400,000 U/kg s.c.) prior to induction of colitis and they were decapitated 24 h (acute group) or 6 days (chronic group) after the induction of colitis (each group consists of eight to ten rats). Pretreatment with the antioxidants reduced the macroscopic damage score significantly in both acute and chronic groups compared with untreated colitis groups, whereas they reduced the microscopic damage score and colonic wet weight only in the chronic group. The chemiluminescence assay -a technique to assess the presence of reactive oxygen species in the tissues -values of the groups pretreated with the antioxidants showed a tendency to decrease compared with the untreated colitis group, but they were not statistically significant. Based on these findings, pretreatment with the antioxidants superoxide dismutase or catalase has beneficial effects on the extent of colonic inflammation, particularly in the chronic period, and this may support the importance of antioxidant therapy to reduce the severity of inflammatory bowel disease in humans.