Oxidative Stress Markers in Intestinal Mucosa of Tunisian Inflammatory Bowel Disease Patients

Background/Aims:

Inflammatory bowel diseases (IBDs), Crohn''s disease (CrD) and ulcerative colitis (UC), are chronic gastrointestinal inflammatory disorders. The precise etiology of IBD remains unclear, and it is thought that interactions among various factors, including, genetic factors, the host immune system and environmental factors, cause disruption of intestinal homeostasis, leading to dysregulated inflammatory responses of the gut. As inflammation is intimately related to formation of reactive intermediates, including, reactive oxygen species, oxidative stress has been proposed as a mechanism underlying the pathophysiology of IBD. The purpose of this study is to examine the lipid peroxidation, protein oxidation and anti-oxidative profile in Tunisian IBD.

Materials and Methods:

Malondialdehyde (MDA), conjugated dienes (CD), protein thiol levels, as well as the catalase (CAT) activity were evaluated in intestinal biopsies of 17 patients affected by IBD (12 CrD and 5 UC) and 12 healthy control individuals.

Results:

Oxidative stress was confirmed in these two types of disease biopsies as compared to controls. MDA and CD levels were significantly increased in both UC and CrD patients’ biopsies as compared to controls’ biopsies (P < 0.001). CAT activity was similar in UC and CrD biopsies’ and was not significantly increased in IBD patients’ biopsies compared with controls’ biopsies (P > 0.05). Anon-significant decrease in thiol (SH) level was observed in both UC and CrD patients’ biopsies compared with controls’ biopsies (P > 0.05).

Conclusion:

Increased levels of MDA and CD in IBD patients’ biopsies underline the implication of oxidative stress in the physiopathology of IBD.     

Inflammation-Related Erythrocyte Aggregation in Patients with Inflammatory Bowel Disease

Chronic inflammation is associated with increased erythrocyte adhesiveness/aggregation. This might have deleterious effects on the microcirculatory flow and tissue oxygenation. We aimed to determine the degree of erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with inflammatory bowel disease (IBD). Fifty-two patients (24 women and 28 men) with ulcerative colitis (UC) at a mean age of 44.0 ± 16.8 years and 96 patients (44 women and 52 men) with Crohns disease (CD) at a mean age of 38.0 ± 15.5 years, with various degrees of disease activity, were matched to normal controls. A simple slide test and image analysis were used to determine the degree of erythrocyte adhesiveness/aggregation. CD activity index (CDAI) was determined in patients with CD, while clinical colitis activity index was applied for patients with UC. A significant (P < 0.0005) increment in the degree of erythrocyte adhesiveness/aggregation was noted in both groups of IBD patients compared with matched control groups. This increment was evident even in individuals with a low index of disease activity and during remission. The highly significant correlation with the concentrations of fibrinogen suggests that the degree of erythrocyte adhesiveness/aggregation is an inflammation-related phenomenon. An enhanced state of erythrocyte adhesiveness/aggregation was noted in the peripheral blood of patients with IBD. This might have a deleterious effect on intestinal microcirculatory flow and tissue oxygenation.     

The Implications of Oxidative Stress and Antioxidant Therapies in Inflammatory Bowel Disease: Clinical Aspects and Animal Models

Inflammatory bowel disease (IBD), including Crohn''s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder characterized by alternating phases of clinical relapse and remission. The etiology of IBD remains largely unknown, although a combination of patient''s immune response, genetics, microbiome, and environment plays an important role in disturbing intestinal homeostasis, leading to development and perpetuation of the inflammatory cascade in IBD. As chronic intestinal inflammation is associated with the formation of reactive oxygen and reactive nitrogen species (ROS and RNS), oxidative and nitrosative stress has been proposed as one of the major contributing factor in the IBD development. Substantial evidence suggests that IBD is associated with an imbalance between increased ROS and decreased antioxidant activity, which may explain, at least in part, many of the clinical pathophysiological features of both CD and UC patients. Hereby, we review the presently known oxidant and antioxidant mechanisms involved in IBD-specific events, the animal models used to determine these specific features, and also the antioxidant therapies proposed in IBD patients.Key Words: Animal models, antioxidants, Crohn''s disease, lipid peroxidation, reactive oxygen species, ulcerative colitis     

Oxidative DNA Damage and Antioxidant Activity in Patients with Inflammatory Bowel Disease

Chronic inflammation may contribute to cancer risk through the accumulation of specific products as a result of DNA damage. Endogenous antioxidant enzymes prevent the formation of these harmful products. Oxidative DNA damage and endogenous antioxidant defense were determined in patients with inflammatory bowel disease (IBD). Plasma levels of 8-hydroxydeoxyguanosine (8-OHdG) and nitric oxide (NO) and plasma activities of glutathione peroxidase (G-Px) and superoxide dismutase (SOD) were determined in patients with IBD by ELISA and spectrophotometric assay, respectively. Plasma levels of 8-OHdG, SOD, and G-Px activity were found to be increased in the patient group compared to the control group (P < 0.02, P < 0.001, and P < 0.001, respectively), whereas NO was unchanged. 8-OHdG level was found to be weakly correlated with age, NO, and SOD. The results show increased DNA damage in patients with IBD. This may explain the increased risk of developing colon cancer in these patients.     

Reduced Plasma Antioxidant Concentrations and Increased Oxidative DNA Damage in Inflammatory Bowel Disease

Background: Oxidative stress is believed to play a key role in the pathogenesis of inflammatory bowel disease (IBD)-related intestinal damage. Circulating antioxidants may have a role to play in preventing free radical-mediated tissue injury. Methods: Plasma vitamin A, E and carotenoid concentrations, leukocytic genomic damage and 8-hydroxy-deoxy-guanosine (8-OHdG) concentration were determined in 46 ulcerative colitis (UC) patients, 37 Crohn disease (CD) patients and 386 controls. A 20 ml blood sample was taken from each subject for antioxidant and 8-OHdG measurements. A food frequency questionnaire was administered to a sample of subjects from each group to evaluate daily intake of dietary compounds. Results: Antioxidant concentration was significantly reduced in IBD patients, particularly in those with active disease, with respect to controls ( P < 0.0001). 8-OHdG concentrations were significantly increased in IBD patients compared to controls, independent of disease activity ( P < 0.05). No correlation was found between antioxidant and 8-OHdG concentrations. Carotenoid concentrations were significantly reduced in malnourished IBD patients (0.89 ± 0.14 μmol/l) compared to patients with normal or high body mass index (1.83 ± 0.12 μmol/l; P < 0.05), independent of disease activity or extension. Protein, fruit and vegetable intakes of IBD patients were significantly lower than those of controls. Conclusions: Depletion of antioxidants is likely to be important in the pathophysiology of IBD: UC and CD patients show increased free radical peripheral leukocyte DNA damage and decreased plasma antioxidant defenses. These results indicate the necessity of further studies to establish whether optimal vitamin status may improve the clinical course of UC and CD.     

The Fatty Acid Profile of the Erythrocyte Membrane in Initial-Onset Inflammatory Bowel Disease Patients

Background and Objectives

The sudden change in the dietary habits of the Japanese population towards a European/American-style diet since the 1960s is thought to be responsible for the recent increase in the incidence of inflammatory bowel disease (IBD) in Japan. Dietary fatty acid intake influences the fatty acid profiles of vital cell membranes, which might be a source of inflammatory mediators.

Methods

We investigated the fatty acid composition of the erythrocyte membrane in 90 healthy Japanese and 43 initial-onset IBD patients (ulcerative colitis, UC: 25; Crohn’s disease, CD: 18) who had not undergone any dietary intervention to examine the role fatty acids play in the onset of IBD.

Results

The erythrocyte membrane n-3/n-6 ratio of the initial-onset IBD patients was 0.42 ± 0.13, which was not significantly different from that of the healthy Japanese subjects (0.41 ± 0.13). However, the CD patients displayed a significantly lower mean percentage weight (MPW) of linoleic acid (LA) than the healthy subjects (8.25 ± 1.75 vs. 9.90 ± 1.29; p < 0.001), while their MPW of arachidonic acid (AA) was significantly higher than those of the healthy subjects and UC patients (11.22 ± 2.18 vs. 9.76 ± 1.64, p < 0.01; vs. 9.58 ± 1.97, p < 0.01, respectively). The mean delta 6-desaturation index of the CD patients was significantly higher than that of the healthy subjects (1.61 ± 0.65 vs. 1.11 ± 0.26; p < 0.001).

Conclusions

The CD patients displayed significantly higher and lower MPW of AA and LA, respectively, than the healthy subjects, suggesting that delta 6-desaturase is hyperactivated in CD. The cell membrane fatty acid profile might be a therapeutic target in CD.     

Osteoporosis in Inflammatory Bowel Disease

Osteoporosis commonly afflicts patients with inflammatory bowel disease, and many factors link the 2 states together. A literature review was conducted about the pathophysiology of osteoporosis in relation to inflammatory bowel disease. Screening guidelines for osteoporosis in general as well as those directed at patients with inflammatory bowel disease are reviewed, as are currently available treatment options. The purpose of this article is to increase physician awareness about osteopenia and osteoporosis occurring in patients with inflammatory bowel disease and to provide basic, clinically relevant information about the pathophysiology and guidelines to help them treat these patients in a cost-effective manner.     

Inflammatory Bowel Disease and Myositis

A patient with Crohn’s disease developed proximal muscle weakness, increased serum creatine phosphokinase activity and electromyographic abnormalities. A muscle biopsy was non-diagnostic. Although rare, myositis should be included in the differential diagnosis of muscle weakness in patients with inflammatory bowel disease. Received: 30 July 1998 / Accepted: 26 January 1999     

Atopy in Inflammatory Bowel Disease

Thirty-nine patients with ulcerative colitis and 35 with Crohn's disease have been investigated for evidence of reaginic hypersensitivity and compared with control subjects. There was no difference in the frequency of a personal or family history of atopy or in serum IgE levels. Similarly, no overall difference was noted in prick test responses to 21 allergens. However, further analysis of prick test responses showed that patients with inflammatory bowel disease responded more frequently to food allergens. This was highly significant when compared with healthy controls (p < 0.001). The relevance of this finding to the aetiology of inflammatory bowel disease is discussed.