Analysis of Oxidative Stress-Related Markers in Crohn’s Disease Patients at Surgery and Correlations with Clinical Findings

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.

Effect of Dipeptidyl-Peptidase 4 Inhibitors on Circulating Oxidative Stress Biomarkers in Patients with Type 2 Diabetes Mellitus

“…Conversely, studies focused on the evaluation of a single oxidative damage marker may give incomplete information on the overall redox status. Notably, we measured various biomarkers reflecting oxidative damage to the main macromolecules such as lipids (TBARS), proteins (carbonyl residues and AOPPs) and DNA (Fpg sites) and found positive correlations among almost all of them, in line with our previous results [35].…”

“…This prevents any analysis on possible effects of hyperglycemia on oxidative stress. It is also important to highlight that the levels of oxidative stress biomarkers in the entire cohort of T2DM patients did not significantly differ from those measured in the serum of healthy controls [35]. We demonstrated previously that significant differences in FRAP levels were seen between heathy controls and poorly controlled T2DM patients but not between heathy controls and T2DM patients with good glycemic control [36]; similarly, Morsi et al [37] did not find significant differences in malondialdehyde (MDA) levels between controls and well controlled T2DM patients.…”

Time-Dependent Indirect Antioxidative Effects of Oat Beta-Glucans on Peripheral Blood Parameters in the Animal Model of Colon Inflammation

“…Reactive oxygen species playing immunoregulatory functions in IBD patients may contribute to the initiation and/or progression of disease [8]. The overproduction of ROS associated with increased activation of immune cells induces a pathogenic cascade, which consequently intensifies inflammation and leads to oxidative damage to DNA, proteins and lipids [9]. Therefore, it is important to identify oxidative stress markers sensitive to therapeutic factors and supporting IBD therapy, which may not only have local effects on the gut-associated lymphoid tissue but may also have systemic effects.…”

Intestinal Epithelial Cells Respond to Chronic Inflammation and Dysbiosis by Synthesizing H2O2

“…Inflammatory bowel diseases are characterized by dysbiosis, disproportionate immune responses against the microbiota, and high levels of ROS (McKenzie et al, 1996; Gitter et al, 2001; Hussain et al, 2003; Itzkowitz and Yio, 2004; Tamboli et al, 2004; Luceri et al, 2019). Even though the high oxidative stress in IBD patients is likely due to the oxidative burst of infiltrating neutrophils, epithelial Nox1 and Duox2 are overexpressed in IBD patient biopsies (MacFie et al, 2014; Chu et al, 2017).…”