Nitric oxide as a potential biomarker in inflammatory bowel disease

Abstract

The aim of this study was to investigate changes in serum nitric oxide (NO) concentration in inflammatory bowel diseases (IBD) patients and its use as potential biomarker in differential diagnosis of ulcerative colitis (UC) and Crohn's disease (CD) and in disease activity assessment. In 60 patients of both genders - 30 with ulcerative colitis and 30 with Crohn's disease - and 30 controls serum nitric oxide concentration was determined by measuring nitrite concentration, a stable metabolic product of NO with oxygen. Conversion of nitrates (NO3-) to nitrites (NO2-) was done with elementary zinc. The nitrite concentration was determined by classic colorimetrical Griess reaction. Median serum NO concentration was statistically different (p=0,0005) between UC patients (15.25 µmol/L; 13.47 - 19.88 µmol/L), CD patients (14.54 µmol/L; 13.03 -16.32 µmol/L) and healthy controls (13.29 µmol/L; 12.40 - 13.92 µmol/L). When active UC and CD patients were compared with inactive UC and CD patients respectively a significant difference in serum NO level was found (p=0.0005). With a cut-off level of 17.39 µmol/L NO had a sensitivity of 100% and a specificity of 100% in discriminating between active and inactive UC patients. With cut-off value of 14.01 µmol/L serum NO level had a sensitivity of 88% and a specificity of 69% in distinguishing between patients with active CD and inactive CD. Serum NO concentration is a minimally invasive and rapid tool for discriminating between active and inactive IBD patients and could be used as useful biomarker in monitoring of disease activity in IBD patients.

Overview of cytokines and nitric oxide involvement in immuno-pathogenesis of inflammatory bowel diseases

“…Our study [16,17] showed significantly higher serum levels of NO in CD patients compared to UC patients. However, data from previous studies reported no significant differences between these two categories of disease, whereas higher systemic levels of NO in UC compared to CD was found [16,17,26,29] . A significant difference was observed in the NO concentrations between the active and inactive phase of the disease.…”

“…This observation suggests a possible use of serum NO levels for monitoring disease activity in both types of IBD [16,28,29] . While several studies conducted using animal models indicate the deleterious effect of NO, recent studies have shown that NO may also exert a protective effect against colitis [29][30][31][32] . One study conducted using a DSSinduced colitis model found that nitrite administration exerts both preventive and therapeutic effects in colonic inflammation [33] .…”

“…The deleterious role of NO in IBD was proposed after clinical studies reported the presence of a high levels of nitrite/nitrate in the plasma, urine, and the lumen of the colon [26][27][28] . Moreover, a correlation between the overexpression of iNOS, the increased concentration of NO, and the severity of diseases was shown [29] . In fact, increased levels of NO were found in the serum, stool, and urine of patients in the active phase of UC and CD compared to those in the inactive phase [26,29] .…”

“…Moreover, a correlation between the overexpression of iNOS, the increased concentration of NO, and the severity of diseases was shown [29] . In fact, increased levels of NO were found in the serum, stool, and urine of patients in the active phase of UC and CD compared to those in the inactive phase [26,29] . Our study [16,17] showed significantly higher serum levels of NO in CD patients compared to UC patients.…”

Elevated Serum C-Reactive Protein Level Is Not Associated With Serum Nitric Oxide in Patients With Posttraumatic Stress Disorder

“…In certain conditions, NO would produce peroxynitrite contributing to cell cytotoxicity and tissue damage and up-regulation of the inflammatory response. In fact an excess of NO is involved in pathophysiology of numerous diseases, including cardiovascular and metabolic diseases (Omar et al 2016), kidney disease (Orida & Lai 2000), inflammatory bowel disease (Avdagi et al 2013), neurological diseases (Ibragic et al 2012), many tumors (Vannini et al 2015) etc.…”