Review article: the role of oxidative stress in pathogenesis and treatment of inflammatory bowel diseases - PubMed (original) (raw)

Review

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

Aleksandra Piechota-Polanczyk et al. Naunyn Schmiedebergs Arch Pharmacol. 2014 Jul.

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.

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Figures

Fig. 1

Fig. 1

Formation of ROS and anti-oxidant defence system in intestinal epithelial cells. CAT catalase, GRd glutathione reductase, GSH reduced glutathione, GSSG oxidised glutathione, GPx glutathione peroxidise, H 2 O 2 hydrogen peroxide, NO • nitric oxide, NOX NADPH oxidase, ONOO − peroxynitrate, O 2 •− superoxide anion, OH • hydroxyl radical, SOD1 cooper/zinc superoxide dismutase, SOD2 mitochondrial superoxide dismutase, SOD3 extracellular superoxide dismutase, XO xanthine oxidase. Numbers corresponds to reactions catalysed by representative enzymes and presented in Table 2

Fig. 2

Fig. 2

The influence of ROS and cytokines on signalling pathways in intestinal epithelial cells. AGE advanced glycation end products, AP-1 activator protein 1, ICAM intracellular adhesion molecule, IL-6 interleukin 6, IL-6R interleukin 6 receptor, iNOS inducible nitric oxide synthase, NF-kB nuclear factor-kappa B, NOX NADPH oxidase, MAPK mitogen-activated protein kinases, OCl − hypochlorite ion, SOD3 extracellular superoxide dismutase, TNF-α tumour necrosis factor alpha, TNFR tumour necrosis factor receptor

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