Role of oxidative stress and antioxidant enzymes in Crohn's disease

Abstract

There is increasing interest in oxidative stress being a potential aetiological factor and/or a triggering factor in Crohn's disease, rather than a concomitant occurrence during the pathogenesis of the disease. Recent research has shown that the immune mononuclear cells of Crohn's disease patients are induced to produce hydrogen peroxide (H2O2). Similarly, the regulation of antioxidant enzymes during disease in these cells has been unravelled, showing that SOD (superoxide dismutase) activity and GPx (glutathione peroxidase) activity is increased during active disease and returns to normal in remission phases. However, catalase remains constantly inhibited which supports the idea that catalase is not a redox-sensitive enzyme, but a regulator of cellular processes. ROS (reactive oxygen species) can be produced under the stimulus of different cytokines such as TNFα (tumour necrosis factor α). It has been shown in different experimental models that they are also able to regulate apoptosis and other cellular processes. The status of oxidative stress elements in Crohn's disease and their possible implications in regulating cellular processes are reviewed in the present paper.

Oxidative Stress: An Essential Factor in the Pathogenesis of Gastrointestinal Mucosal Diseases

“…Altered mesenteric circulation, intestinal microcirculation, and intestinal ischemia are potential etiologic factors in IBD, although their involvement could be secondary (127). The association of ROS with IBD is evident from the observation that increased ROS and decreased antioxidant levels contribute toward major pathogenic mechanisms in IBD (58,126 (186) and "in IBD, the fuse appears to be lit" (42).…”

“…Catalase-expressing pathogens such as Campylobacter jejuni (10), H. pylori (198), Helicobacter hepaticus (95), and enterobacteriaceae family bacteria (281) (196). Crohn's disease patients show permanent suppression of catalase activity in their mononuclear cells (126). Genetically modified Lactobacilli capable of producing catalase have been shown to reduce tumor in colon (75) and colitis in mice (166).…”

Synthetic Oleanane Triterpenoids: Multifunctional Drugs with a Broad Range of Applications for Prevention and Treatment of Chronic Disease

“…Because activation of the Nrf2 pathway is cytoprotective in the colon (Khor et al, 2006;Theiss et al, 2009) and CDDO-Im induces transcription of Nrf2-target genes such as NQO1 and GCLC in the stomach, small intestine, and colon (Yates et al, 2007), the SOs should also be effective against conditions such as Crohn's disease, inflammatory bowel disease, and ulcerative colitis. In these diseases, oxidative stress and inflammation can drive pathogenesis (Iborra et al, 2011;Strober and Fuss, 2011).…”

Role of metallothionein in murine experimental colitis

“…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 stress-related pathogenesis of IBDs.…”