Abstract
IBD results from activation of the gastrointestinal immune system toward gut microbiota in genetically susceptible individuals. Oxidative stress signalling plays a role in IBD development and exacerbation as it leads among others to mucosal barrier damage. Reduction of oxidative stress may preserve gut microbiota and control inflammation. We assessed the concentrations of free thiols (FT) and uric acid (SUA), constituting together a large part of non-enzymatic serum antioxidant capacity, with reference to IBD phenotype, activity, inflammatory markers, advanced oxydation protein products (AOPP) and as mucosal healing (MH) markers. A study group consisted of 175 individuals: 57 controls, 71 UC, and 47 CD patients. The disease activity was assessed using the Crohn's Disease Activity Index (CDAI) for CD and Rachmilewitz Index (RI) as well as Mayo Endoscopic Score for UC. SUA and FT concentrations were measured with uricase method and modified Ellman's method, respectively. As compared with controls, SUA concentrations were significantly lower in patients with CD but not UC. Detailed analysis demonstrated that SUA concentrations were significantly lower in both active CD and UC. In CD patients with active disease, SUA concentrations inversely correlated with CDAI (ρ = −0.35, p = 0.038). As compared with controls, FT concentrations were significantly lower in patients with both CD and UC, regardless the disease activity. There were no significant differences between CD and UC or patients with active and inactive disease. However, in CD and UC patients with active disease, FT concentrations were inversely correlated with, respectively, CDAI (ρ = −0.52, p = 0.001) and RI (ρ= −0.40, p = 0.044). In UC patients, SUA (ρ = −0.41, p < 0.001) and FA (ρ = −0.27, p = 0.023) concentrations were inversely correlated with the severity of bowel inflammation expressed in terms of Mayo endoscopic score with a significant drop between score 3 and scores 0 and 1. As MH markers, SUA displayed better overall accuracy, expressed in terms of area under ROC curve, and higher specificity than FA. Exclusively in patients with UC, SUA inversely but weakly correlated with IL-1 (ρ = −0.25, p = 0.035) and FT with TNF-α (ρ = −0.38, p = 0.044). In patients with active CD, FA was correlated with hsCRP (ρ = −0.56, p < 0.001), ESR (ρ = −0.51, p = 0.003), PLT (ρ = −0.45, p = 0.008), and IL-6 (ρ = −0.45, p = 0.008). Solely FT, in patients with active CD, inversely correlated with AOPP (ρ = −0.45, p = 0.007). Free thiol content, particularly in patients with active CD, was inversely related to various inflammatory markers as well as to AOPP, important marker of oxidative stress. Free thiol status and uric acid were decreased in IBD and correlated with severity of inflammation in UC.
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