Review article: the role of oxidative stress in pathogenesis and treatment of inflammatory bowel diseases

Abstract

In this review, we focus on the role of oxidative stress in the aetiology of inflammatory bowel diseases (IBD) and colitis-associated colorectal cancer and discuss free radicals and free radical-stimulated pathways as pharmacological targets for anti-IBD drugs. We also suggest novel anti-oxidative agents, which may become effective and less-toxic alternatives in IBD and colitis-associated colorectal cancer treatment. A Medline search was performed to identify relevant bibliography using search terms including: ‘free radicals,’ ‘antioxidants,’ ‘oxidative stress,’ ‘colon cancer,’ ‘ulcerative colitis,’ ‘Crohn’s disease,’ ‘inflammatory bowel disease.’ Several therapeutics commonly used in IBD treatment, among which are immunosuppressants, corticosteroids and anti-TNF-α antibodies, could also affect the IBD progression by interfering with cellular oxidative stress and cytokine production. Experimental data shows that these drugs may effectively scavenge free radicals, increase anti-oxidative capacity of cells, influence multiple signalling pathways, e.g. MAPK and NF-kB, and inhibit pro-oxidative enzyme and cytokine concentration. However, their anti-oxidative and anti-inflammatory effectiveness still needs further investigation. A highly specific antioxidative activity may be important for the clinical treatment and relapse of IBD. In the future, a combination of currently used pharmaceutics, together with natural and synthetic anti-oxidative compounds, like lipoic acid or curcumine, could be taken into account in the design of novel anti-IBD therapies.

Relationship Between Bilirubin Level and Disease Activity in Crohn’s Disease

“…Increased ROS affects intracellular signals that regulate processes such as cell growth, differentiation and cell death, and increases oxidative stress [11,12]. In studies conducted in Crohn's disease patients it has been shown that oxidative stress is increased by ROS during the activation period [13,14]. In another study done by Maor et al, it was found that oxidative stress increases while the antioxidant capacity decreases during the activation period of Crohn's disease [13].…”

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“…[37,38] ROS attack the cellular macromolecules, thus disrupting epithelial integrity and hindering mucosal recovery, especially in the case of impaired endogenous defense systems. [39] Excessive generation of ROS leads to various pathological processes such as inflammation.…”

Antioxidant Supplements and Gastrointestinal Diseases: A Critical Appraisal

“…Catalase and superoxide dismutase levels are also altered in some models [34] . The gene ablation of inducible NO synthase (iNOS) in mice showed significant attenuation of UC indicating that iNOS and NO play a major role in UC [35] . In UC, the inflamed human lamina propria showed an increased O, open, R, random, B, blind, DB, double blind, C, controlled, P, placebo controlled.…”

“…infiltration by neutrophils and myeloperoxidase activity [24] . At early stages of CD, there is a patchy necrosis of leukocytes near the crypts and an increased number of macrophages and granulocytes [35] . These phagocytotic cells produce large amounts of NO and superoxide, resulting in the formation of peroxynitrite which can cause tyrosine nitration and also cause DNA damage.…”