Crohn’s Disease in Clinical Remission Is Marked by Systemic Oxidative Stress

Abstract

Introduction: Crohn’s disease (CD) is characterized by chronic and relapsing inflammation of the gastro-intestinal tract. It is assumed that oxidative stress contributes to CD pathogenesis, but systemic biomarkers for oxidative stress in CD are not yet identified. A reduction in free thiol groups in plasma proteins (“plasma free thiols”) reflects systemic oxidative stress since they are prime substrates for reactive oxygen species. Here, we determined the concentrations of plasma free thiols in CD patients and healthy controls and studied the putative correlation with disease parameters. Methods: Free thiols were quantified in plasma of patients with CD in clinical remission [according to the Harvey Bradshaw Index (HBI)] and healthy controls and adjusted for plasma albumin. Albumin-adjusted free thiol concentrations were analyzed for associations with clinical and biochemical disease markers. Results: Mean plasma free thiol concentrations were significantly lower in patients with CD ( n = 51) compared to healthy controls ( n = 27) (14.7 ± 2.4 vs. 17.9 ± 1.8 μmol/g albumin; P < 0.001). Patients with CD with above-average free thiols had significantly lower CRP levels (median 1.4 [interquartile range] [0.4; 2.6] vs. 3.6 [0.6; 7.0] mg/L; P < 0.05) and BMI (23.6 ± 4.8 vs. 27.1 ± 5.2 kg/m 2 ; P < 0.05). Patients with CD having solely colonic disease demonstrated markedly reduced plasma free thiol concentrations compared to patients with ileocolonic involvement (13.2 ± 1.8 vs. 15.2 ± 2.2 μmol/g; P < 0.05). Finally, plasma free thiol concentrations negatively correlated with biomarkers of inflammation, including hsCRP, SAA, IL-17A (all P < 0.05), and VEGF. Conclusion: Plasma free thiols are reduced in patients with CD in clinical remission compared to healthy controls. Thus, subclinical CD disease activity is reflected by systemic oxidative stress and plasma free thiols may be a relevant therapeutic target and biomarker to monitor disease activity in CD.

Systemic Oxidative Stress Is Increased in Postmenopausal Women and Independently Associates with Homocysteine Levels

“…Mean serum free thiol concentrations were 780 ± 80.9 µM for reproductive women and 762.9 ± 85.3 µM for menopausal women (p < 0.001 after correction for age, Figure S1). Concentration ranges of serum free thiols were in accordance with previous studies that used the same detection method [20][21][22][23][24]. Median age of reproductive women was 30 years (interquartile range (IQR) 22-42 years), whereas menopausal women had a median age of 54 years (IQR: 50-59 years).…”

Polyphenolic Maqui Extract as a Potential Nutraceutical to Treat TNBS-Induced Crohn’s Disease by the Regulation of Antioxidant and Anti-Inflammatory Pathways

“…CD is characterized by chronic transmural and segmental intestinal inflammation that can affect any part of the gastrointestinal tract. The etiopathogenesis is complex and multifactorial, and is not totally clear yet [ 30 ]. Patients typically experience periods of flare-ups and symptomatic remission, which are difficult to predict and treat adequately [ 31 ].…”

Oxidative Stress Markers in Inflammatory Bowel Diseases: Systematic Review

“…Some authors have found it to drop only in active disease, either because patients in remission had its concentrations at the levels observed in healthy individuals [24] or because only patients in active phase had been enrolled [25,55]. Low albumin concentration is one of the predictors of malnutrition [54] and its decrease in IBD patients, particularly in the active phase of the disease, is likely to reflect the disease-associated worsening of nutritional status. The similar function of an indicator of nutritional status can be fulfilled by transferrin, which also decreases solely in IBD patients with active disease [56] (Table 1).…”

“…Bourgonje et al [54] evaluated albumin-adjusted thiols exclusively in CD patients in remission and observed that their depletion is related to the disease extent, as the index was significantly lower in patients with ileocolonic involvement than colonic. Additionally, it was inversely related with the severity of inflammation.…”