Decrease in two intestinal copper/zinc containing proteins with antioxidant function in inflammatory bowel disease.

Mulder, Theodorus; Verspaget, Hein W.; Janssens, A. R.; Bruin, P.A.F. de; Peña, Amado Salvador; Lamers, C. B. H. W.

doi:10.1136/gut.32.10.1146

Cited by 116 publications

(52 citation statements)

References 32 publications

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“…Mulder et al (36) demonstrated that MT expression was decreased in the colonic mucosa of patients with IBD. Kruidenier et al (37) also reported that patients with IBD had decreased MT expression levels in the colon.…”

Section: Discussionmentioning

confidence: 99%

Role of metallothionein in murine experimental colitis

Tsuji

Naito

Takagi

et al. 2013

International Journal of Molecular Medicine

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Abstract. Metallothioneins (MTs) are a family of cysteine-rich low molecular-weight proteins that can act as reactive oxygen species scavengers. Although it is known that the induction of MT expression suppresses various inflammatory disorders, the role of MTs in intestinal inflammation remains unclear. In this study, we investigated the effects of dextran sulfate sodium (DSS) administration in mice with targeted deletions of the MT-I/II genes. Acute colitis was induced by 2% DSS in male MT-I/II double knockout (MT-null) and C57BL/6 (wild-type) mice. The disease activity index (DAI) was determined on a daily basis for each animal, and consisted of a calculated score based on changes in body weight, stool consistency and intestinal bleeding. Histology, colon length, myeloperoxidase (MPO) activity and colonic mRNA expression and the concentration of inflammatory cytokines were evaluated by real-time-PCR and enzyme-linked immunosorbent assay (ELISA). The localization of MTs and macrophages was determined by immunohistological and immunofluorescence staining. To investigate the role of MTs in macrophages, peritoneal macrophages were isolated and their responses to lipopolysaccharide were measured. Following DSS administration, the DAI score increased in a time-dependent manner and was significantly enhanced in the MT-I/II knockout mice. Colonic MPO activity levels and inflammatory cytokines [tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-17] production increased following DSS administration, and these increases were significantly enhanced in the MT-I/II knockout mice compared with the wild-type mice. MT-positive cells were detected in the lamina propria and submucosal layer by immunohistochemical and immunofluorescence staining, and were mainly co-localized in F4/80-positive macrophages. The production of inflammatory cytokines (TNF-α, IFN-γ and IL-17) from isolated peritoneal macrophages increased following lipopolysaccharide stimulation, and these increases were significantly enhanced in the macrophages obtained from the MT-I/II knockout mice. These data indicate that MTs play an important role in the prevention of colonic mucosal inflammation in a mouse model of DSS-induced colitis, thus suggesting that endogenous MTs play a protective role against intestinal inflammation. IntroductionInflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn's disease are known as refractory and recurrent diseases of the gastrointestinal tract. Although the features of IBDs suggest a number of possible causes, including genetic, infectious and immunological factors, the precise pathogenesis of IBDs remains unknown (1-3). Recent evidence suggests that oxidative stress caused by reactive oxygen species (ROS) is an important factor involved in the onset and development of intestinal inflammation. Furthermore, it has also been demonstrated that disruptions in the antioxidant defense system are involved in the pathophysiology of IBDs (4,5). Therefore, it is important to investigate the oxidative s...

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Section: Discussionmentioning

confidence: 99%

Role of metallothionein in murine experimental colitis

Tsuji

Naito

Takagi

et al. 2013

International Journal of Molecular Medicine

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“…The loss of antioxidant defenses may severely compromise the inflamed mucosa and render it more susceptible to the oxygen-induced injury and thereby hinder the recovery of the mucosa and the return of the integrity of the epithelial cell layer. Thus, it increased the intestinal mucosal permeability [27,28] , while antioxidants treatment is beneficial to ameliorate intestinal mucosa permeability [29 -34] . In the present study, balsalazine attenuated intestinal oxidative damage markedly by decreasing MDA content, along with increasing SOD and GSH-Px activity.…”

Section: Discussionmentioning

confidence: 99%

Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice

Liu

Qiao

et al. 2009

Acta Pharmacol Sin

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Aim:To investigate the effect of balsalazine treatment on intestinal mucosal permeability in dextran sulfate sodium (DSS)-induced colitis and to determine the mechanism of the balsalazine-induced changes. Methods: Experimental colitis was induced in C57BL/6J mice by the administration of 5% DSS. Balsalazine was administered intragastrically at doses of 42, 141, and 423 mg/kg. The disease activity index (DAI) score was evaluated and colon tissue was collected for the assessment of histological changes. The amount of malondialdehyde (MDA) in the colon was determined, along with the activity of myeloperoxidase (MPO), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Mucosa from the small intestine was collected to determine the levels of tumor necrosis factor (TNF)-α and interferon (IFN)-γ. The mucosa was ultrastructurally examined with transmission electron microscopy and intestinal permeability was assayed using Evans blue. Results: Balsalazine was found to reduce the DAI score and the histological index (HI) score, decrease the MDA content and the activity of MPO, and increase the activity of SOD and GSH-Px in colitis mice. At the same time, balsalazine ameliorated microvillus and tight junction structure, resulting in a decrease in the amount of Evans blue permeating into the intestinal wall and the levels of TNF-α and IFN-γ in colitis mice. Conclusion: In colitis mice, the anti-colitis effect of balsalazine results in a decrease in intestinal mucosal permeability. The mechanism of this effect is partly associated with balsalazine's antioxidative and anti-inflammatory effects.

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“…It has been reported that oxygen free radicals are related to a deterioration in inflammatory bowel disease (IBD) (1)(2)(3). Therefore, radical scavengers such as super oxide dismutase (SOD) were expected to be therapeutic drugs for IBD; however, to date, none have been put to practical use.…”

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confidence: 99%

Effect of Lecithinized-Superoxide Dismutase on the Rat Colitis Model Induced by Dextran Sulfate Sodium.

et al. 1997

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ABSTRACT-Lecithinized-superoxide dismutase (PC-SOD), which is synthesized with a lecithin derivative bound covalently to recombinant human Cu,Zn-SOD, has a longer half-life in blood and higher cell affinity than unmodified SOD. The effects of PC-SOD were evaluated using the rat ulcerative colitis model induced by 3% dextran sulfate sodium. Intravenous injection of rats with 0.5 or 1 mg/kg of PC-SOD suppressed the progression of bloody stools, the formation of erosion, and the infiltration of the colon with inflammatory cells. Furthermore, it also reduced the increase of leukocytes in blood. Thus, PC-SOD may have therapeutic potential in the treatment of ulcerative colitis.

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Decrease in two intestinal copper/zinc containing proteins with antioxidant function in inflammatory bowel disease.

Cited by 116 publications

References 32 publications

Role of metallothionein in murine experimental colitis

Role of metallothionein in murine experimental colitis

Balsalazine decreases intestinal mucosal permeability of dextran sulfate sodium-induced colitis in mice

Effect of Lecithinized-Superoxide Dismutase on the Rat Colitis Model Induced by Dextran Sulfate Sodium.

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