Oxygen radicals in ulcerative colitis

Abstract

This article reviews the pathophysiologic concept that superoxide and hydrogen peroxide, generated by activated leukocytes, together with low-molecular-weight chelate iron derived from fecal sources and from denatured hemoglobin, amplify the inflammatory response and subsequent mucosal damage in patients with active episodes of ulcerative colitis. The putative pathogenic mechanisms reviewed are as follows: ( l ) Dietary iron is concentrated in fecal material owing to normally limited iron absorption. (2) Mucosal bleeding, characteristic of ulcerative colitis, as well as supplemental oral iron therapy for chronic anemia, further conspire to maintain or elevate mucosal iron concentration in colitis. (3) Fenton chemistry, driven especially by leukocyte-generated superoxide and hydrogen peroxide, leads to formation of hydroxyl radicals. (4) The resultant oxidative stress leads to the extension and propagation of crypt abscesses, either through direct membrane disruption by lipid peroxidation or through generation of secondary toxic oxidants such as chloramines. (5) Chemotactic products of lipid peroxidation, including 4-hydroxynonenal, provide positive feedback to accelerate this inflammatory/oxidative process, leading to acute exacerbations of the disease. (6) Other oxidized products, such as oxidized tryptophan metabolites, created by free radical mechanisms in or near the mucosa, may act as carcinogens or tumor promotors that contribute to the exceedingly high incidence of colon carcinoma in patients suffering from chronic ulcerative colitis. In this way, self-sustaining cycles of oxidant formation may amplify flare-ups of inflammation and mucosal injury in ulcerative colitis. This concept, if proved correct by subsequent research, would provide a rationale for several novel clinical approaches to the management of ulcerative colitis, including use of SOD mimetics, iron chelators, and chain-breaking antioxidants.

Protective effects ofRheum tanguticumpolysaccharide against hydrogen peroxide-induced intestinal epithelial cell injury

“…Apoptotic cell death is accompanied with activation of various cell death pathways including caspases, ceramide, altered gene expression, mitochondrial dysfunction and consumption of ATP [4,5] . Although these signals and metabolic events may be important in the regulation of cell death, cell death pathways are also associated with the secondary production of oxidants that appears to contribute to the magnitude of cell death.…”

“…Mucosal lesion in inflammatory bowel disease (IBD) is characterized by dense inflammatory cell infiltrate mainly comprised of neutrophils, macrophages and lymphocytes. Although many inflammatory mediators secreted by these cells, including cytokines IL-1, IL-6, IL-8, IL-10, TNF- and leukotrienes together with luminal bacterial products such as bacterial lipopolysaccharide (LPS) and chemotactic peptide fMLP, have been implicated in the mucosal injury observed in IBD [3] , and the molecules that mediate tissue damage remain poorly understood [4][5][6][7] . Recent indirect evidence has, however, implicated reactive oxygen and nitrogen species (RONS) such as nitric oxide (NO), superoxide (O 2 -), peroxynitrite (ONOO -), hydrogen peroxide (H 2 O 2 ), and hypochlorite (OCl -) in the pathogenesis of mucosal lesion [8][9][10][11] .…”

Update on the pathogenesis of complex regional pain syndrome: Role of oxidative stress

“…10 The cell's water-soluble antioxidants include vitamin C, glutathione peroxidase, SOD, and catalase. [30][31][32][33] It has been speculated that free radical generation by the mitochondrial respiratory chain contributes to the pathophysiology of CRPS I. [34][35][36] Eisenberg et al demonstrated significant increases in malondialdehyde, lactic dehydrogenase, and antioxidants (peroxidase, superoxide dismutase, uric acid) in the serum and especially the saliva of CRPS I patients compared to healthy controls.…”

“…The most important free radicals are oxygen derivatives-particularly superoxide anion (O 2 -•), hydroxyl radical (OH-), and hydrogen peroxide (H 2 O 2 )-and reactive nitrogen species such as nitric oxide and peroxynitrite. 31,32 Therapeutic Approach…”

Therapeutic effects of four molecular-weight fractions of Kurozu against dextran sulfate sodium-induced experimental colitis

“…Our previous study revealed an anti-colitis effect of Kurozu (3), and oxidative and nitration stress are known to be involved in the pathogenesis and severity of UC (4). Therefore, we chromatographically fractionated Kurozu and investigated the protective effects of four molecular-weight fractions against DSS-induced colitis in mice, focusing on anti-oxidative and anti-nitration stress activity.…”