Abstract
Crohn’ disease (CD) patients are at high risk of postoperative recurrence and new tools for the assessment of disease activity are needed to prevent long-term complications. In these patients, the over-production of ROS generated by inflamed bowel tissue and inflammatory cells activates a pathogenic cascade that further exacerbates inflammation and leads to increased oxidative damage to DNA, proteins, and lipids. We measured the products of protein/lipid oxidation and the total antioxidant capacity (ferric reducing ability of plasma, FRAP) in the serum of CD patients with severe disease activity requiring surgery with the aim to characterize their redox status and identify associations between oxidative stress-related markers and their clinical characteristics. At the systemic level, CD was associated with increased levels of protein and lipid oxidation products when compared to healthy volunteers, even though the FRAP values were similar. Advanced oxidation protein product (AOPP) levels showed the highest difference between patients and the controls (11.25, 5.02–15.15, vs. 1.36, 0.75–2.70, median, interquartile range; p < 0.0001) and the analysis of receiver operating characteristic (ROC) curves, indicated for AOPP, the best area under the curve (AUC) value for CD prediction. Advanced glycated end-products (AGEs) were also significantly higher in CD patients (p < 0.01), which is of interest since AOPP and AGEs are both able to activate the membrane receptor for advanced glycation end products (RAGE) involved in inflammatory diseases. Thiobarbituric acid reactive substance (TBARS) levels were significantly higher in CD patients with ileal localization and aggressive disease behavior, in smokers, and in patients suffering from allergies. In conclusion, our data indicate that circulating oxidative stress biomarkers may be attractive candidates as disease predictors as well as for clinical or therapeutic monitoring of CD. Our results also suggest that AOPP/AGEs and RAGE signaling may represent a pathogenic factor and a potential therapeutic target in CD.
Highlights
Crohn’s disease (CD) is a chronic inflammatory disorder of the intestinal tract, with increasing prevalence worldwide [1,2]
This is of interest at least for two reasons: on one hand, circulating biomarkers of oxidative stress offer the advantage of easy collection, low costs, and the possibility to be used on a large scale; on the other hand, the systemic oxidative stress observed in CD may likely contribute to the development of extra-intestinal manifestations such as perianal fistulas, dermatologic diseases, and arthritis, which are very common in these patients [9]
Our results demonstrate an overall increase in oxidative stress biomarkers in CD patients at surgery when compared to the controls, highlighting that severe clinical activity is reflected by systemic oxidative stress
Summary
Crohn’s disease (CD) is a chronic inflammatory disorder of the intestinal tract, with increasing prevalence worldwide [1,2]. One of the main advantages of oxidative modifications of cellular proteins, lipids, and nucleic acids is that they can be measured in the affected intestinal tract, and at the systemic level; several studies have reported increased levels of oxidative stress biomarkers in the serum/plasma of inflammatory bowel disease (IBD) patients [8]. This is of interest at least for two reasons: on one hand, circulating biomarkers of oxidative stress offer the advantage of easy collection, low costs, and the possibility to be used on a large scale; on the other hand, the systemic oxidative stress observed in CD may likely contribute to the development of extra-intestinal manifestations such as perianal fistulas, dermatologic diseases, and arthritis, which are very common in these patients [9]
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