Nonenzymatic Serum Antioxidant Capacity in IBD and Its Association with the Severity of Bowel Inflammation and Corticosteroids Treatment

Abstract

Background and objectives: Oxidative stress signalling plays a monumental role in inflammatory bowel disease (IBD). Reduction of oxidative stress might control inflammation, block tissue damage, and reverse natural history of IBD. We assessed the serum concentrations of free thiols (FT) and uric acid (SUA), together constituting a large part of nonenzymatic serum antioxidant capacity, as well as total antioxidant status (TAS) with reference to IBD phenotype, activity, co-occurrence of anemia, and treatment with azathioprine (AZA) and corticosteroids (CS). Additionally, we appraised the potential of uric acid, thiol stress, and TAS as mucosal healing (MH) markers in ulcerative colitis. Materials and methods: SUA, FT, and TAS were measured colorimetrically using, respectively, uricase, Ellman’s and 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) methods. Results: The study group consisted of 175 individuals: 57 controls, 71 ulcerative colitis (UC), and 47 Crohn’s disease (CD) patients. When compared to controls, SUA levels were significantly lower in patients with CD, and FT and TAS levels were significantly lower in patients with CD and UC. In UC patients, SUA, FT, and TAS inversely correlated with the severity of bowel inflammation. As MH markers, SUA displayed better overall accuracy and higher specificity than FT. In active CD, FT, and SUA were significantly lower in patients with anemia. FT was significantly lower in patients treated with corticosteroids. Conclusions: IBD patients, regardless the disease phenotype, have systemic thiol stress, depleted total antioxidant capacity, and reduced concentrations of uric acid, reflecting, to various degrees, clinical and local disease activity as well as presence of anaemia, the most common extraintestinal manifestation of IBD. Evaluation of systemic total antioxidant status may be useful in noninvasive assessment of mucosal healing. Our findings on thiol stress provide an additional aspect on adverse effects of corticosteroids therapy.

Oxidative Stress Markers in Inflammatory Bowel Diseases: Systematic Review

“…From among non-enzymatic protein antioxidants ( Supplementary Table S3), thiols have been reportedly more markedly depleted in patients with active than inactive IBD [34] and UC, in which they were inversely correlated with clinical activity of the disease expressed in terms of Truelove-Witts score [58]. The association between thiols and IBD activity has been confirmed by Neubauer et al [73], who also reported negative correlation between their concentrations and CDAI/RI and inflammatory indices as well as lack of difference between active and inactive phases of diseases (Table 3). Transferrin, similarly to albumin a negative phase reactant and an index of nutritional status, was also inversely related with the disease activity, being significantly decreased exclusively in CD and UC patients in active phase of the disease.…”

“…No significant association with the disease activity have been reported for Zn and Se, except for one study [82] in which Se concentrations decreased along with UC severity and corresponded with its extension ( Supplementary Table S4). Serum/plasma TAC has been inversely related to inflammatory indices in CD [33,37,72,73] and UC [23,73], although those observations have not been confirmed by all authors [40,71]. It has been also shown by some to be more markedly diminished in active CD [37,71,111] and inversely correlated with indices of its clinical activity [33,35,37,73,111] as well as inversely related to the disease extension in UC [70] (Table 1 and Supplementary Table S4).…”

“…Sampietro et al [72] reported that surgical intervention restored TAS to the levels observed in healthy individuals. It is worth mentioning, that TAS has only recently been found to be a good marker of mucosal healing, as will be further discussed in detail in a section of the review dedicated to the mucosal healing [73] (Table 1). Interestingly, those promising results do not translate into pediatric IBD, which, also consistently, have not seemed to affect TAS concentrations at all [22,35].…”

“…Serum uric acid (SUA) has been determined in IBD patients in four and its saliva level in one paper. It has been found to be decreased in three studies [17,53,73] but to be increased in the remaining two [77,78]. Tian et al [77] calculated that for the highest SUA quartile, the risk for UC manifestation is increased 1.2-fold (Table 1 and Supplementary Table S4).…”

“…As discussed in Section 3.1, based on limited number of articles there is no consensus on uric acid in IBD. Nonetheless, those reporting its reduction in IBD have also shown its inverse relationship with clinical disease activity [53,73] (Table 3 and Supplementary Table S4).…”