Oxidative Stress, Inflammation and Neutrophil Superoxide Release in Patients with Crohn’s Disease: Distinction Between Active and Non-active Disease

Abstract

Increased oxidative stress has been previously demonstrated in patients with Crohn's disease (CD). However, to date, this parameter has not been assessed in a comparative study of patients in prolonged remission and those with the active disease. We report here our study of lipid peroxidation, antioxidant and inflammation status in serum derived from 16 active CD patients, 27 clinically stable patients, and 15 healthy controls. Results The extent of lipid peroxidation was higher in CD patients than in the healthy controls, while the levels of lipid peroxides (PD) and of thiobarbituric acid-reactive substances (TBARS) were significantly (P < 0.01) higher in serum obtained from patients with active CD (22 and 30%, respectively) than in that obtained from patients in remission. An analysis of the antioxidant status revealed that the beta-carotene levels in sera derived from all CD patients - patients with active or stable CD (49.4 +/- 15 and 95.6 +/- 25 mg% beta-carotene, respectively) - were higher than that in the controls (145 +/- 40 mg%). Serum activity of glutathione peroxidase (GSH-Px) was significantly (P < 0.001) higher (by 31%) in the patients with active CD than in the control group. There was no significant difference in GSH-Px activity between patients in remission and the controls. In terms of the inflammatory status, we found significantly (P < 0.01) higher levels of C-reactive proteins (CRP) and of tumor necrosis factor alpha (TNFalpha) in patients with active CD than in CD patients in remission. There was a significant correlation between those parameters and the extent of lipid oxidation. Neutrophils, which are a potential source of oxygen-free radicals, were activated by incubation with phorbol myristate acetate (PMA). Superoxide and lysozyme release were significantly reduced in neutrophils derived from patients with active CD (by 25 and 28%, respectively) in comparison to the control group. However, stimulated neutrophils from stable patients demonstrated only a minimally non-significant lower release of superoxide and lysozyme compared to the controls. Conclusion The results obtained in this study demonstrate an enhanced inflammatory and oxidative stress and a decreased antioxidant status in patients with active CD. As the patients improved and became clinically stable, the oxidative parameters decreased, approaching normal values. As neutrophil activation was also lower in patients with active disease, neutrophil activation may represent a possible defense mechanism of the body against tissue injury.

Relationship Between Bilirubin Level and Disease Activity in Crohn’s Disease

“…Increased ROS affects intracellular signals that regulate processes such as cell growth, differentiation and cell death, and increases oxidative stress [11,12]. In studies conducted in Crohn's disease patients it has been shown that oxidative stress is increased by ROS during the activation period [13,14]. In another study done by Maor et al, it was found that oxidative stress increases while the antioxidant capacity decreases during the activation period of Crohn's disease [13].…”

“…In studies conducted in Crohn's disease patients it has been shown that oxidative stress is increased by ROS during the activation period [13,14]. In another study done by Maor et al, it was found that oxidative stress increases while the antioxidant capacity decreases during the activation period of Crohn's disease [13]. Bilirubin is a product of HEM destruction, which is catalyzed by the HO enzyme.…”

Oxidative Stress: An Essential Factor in the Pathogenesis of Gastrointestinal Mucosal Diseases

“…Enhanced oxidative stress and inflammation in conjunction with decreased antioxidant levels have been reported in patients with active Crohn's disease. However, with improvement of the patient's condition, these parameters of oxidative stress go back to normal levels (178). As NF-B is a major inducer of inflammatory cytokines, the effect of a potent NF-B inhibitor, vanillin, has been studied in mouse model of colitis (325).…”

The Neutrophil Respiratory Burst and Bacterial Digestion in Crohn’s Disease

“…However, enhanced inflammatory and oxidative stress and a decreased antioxidant status were shown in patients with active CD. As the patients improve and become clinically stable, the oxidative parameters decrease, approaching normal values [2]. This is why it is not easy to conclude ''reduced neutrophil count rather than a function'' with these study patients.…”