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

D’Odorico, Anna; Bortolan, S.; Cardin, R.; D’Incà, R.; Martines, Diego; Ferronato, A.; Sturniolo, Giacomo Carlo

doi:10.1080/003655201317097146

Cited by 160 publications

(65 citation statements)

References 25 publications

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“…diclofenac groups. The following hypothesis could explain these findings: (1) the maintenance of tissue antioxidant defense in response to local oxidative stress, which would not occur in a plasmatic level; pro-oxidant activity in tissue, verified in the present work by increase in LOOH and TBARS associated with increase in antioxidant activity showed by increasing SOD levels and maintenance of catalase levels, seems to support this hypothesis; (2) the plasmatic reduction of important antioxidants, such as selenium, vitamins A and E, and carotenoids, which has been attributed in IBD patients to an increase in vascular permeability or in tissue consume [37,38]; in the present study these antioxidants were not measured, but albumin, the most abundant plasmatic protein, showed a significant decrease in the colitis and colitis ? diclofenac groups.…”

Section: Discussionsupporting

confidence: 76%

Decreased Total Antioxidant Capacity in Plasma, but Not Tissue, in Experimental Colitis

et al. 2008

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The aim of the present work was to compare colonic mucosa and plasmatic oxidative stress measured concomitantly and with different degrees of injury in rats with colitis induced by trinitrobenzene sulfonic acid. Three groups were studied: control group, colitis group, and colitis exacerbated by diclofenac. Enzymatic markers of colon injury showed enhanced activity in both groups with colitis. The colitis group treated with diclofenac presented higher colonic damage score than the other groups. In both groups with colitis, higher values of tert butyl hydroperoxide-initiated-chemiluminescence and thiobarbituric acid-reactive substances in tissue and decreased total radical-trapping antioxidant potential (TRAP) levels in plasma were found. In conclusion, independently of the degree of colonic mucosa injury and inflammation, oxidative stress in tissue occurs as a consequence of pro-oxidants increase, and is not explained by a reduction of antioxidant defenses. In both conditions, TRAP determination decreases in plasma, but not in tissue.

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Section: Discussionsupporting

confidence: 76%

Decreased Total Antioxidant Capacity in Plasma, but Not Tissue, in Experimental Colitis

et al. 2008

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“…In inflamed colonic tissue of UC and CC patient samples, representative immunoblot and densitometric analysis data for the antioxidant protein Nrf2 show significant decrease compared to adjacent uninflamed tissue (normal, NL). We should keep in mind that the depletion of systemic antioxidant levels found in IBD patients, 24 can depend on several other factors than different technology technique mentioned earlier herein. Dietary intake may be one of the major causes.…”

Section: Discussionmentioning

confidence: 94%

“…A study by D’Odorico et al 24 analysed the blood circulating antioxidant concentrations in IBD patients and in Ctrl subjects. They found significantly reduced antioxidant saturation in IBD patients, especially in those with active disease, compared to Ctrls ( p< 0.0001 ).…”

Section: Discussionmentioning

confidence: 99%

“…These observations corroborates with several other controversial studies previously reported about antioxidants in active IBD. 24,26 As scientists we need to have a clear understanding that although the results in antioxidant levels among the studies is conflicting, the imperative point is the presence of an imbalance in antioxidant saturation, attesting the fact that vital organs/systems in IBD patients are oxidative stressed.…”

Section: Introductionmentioning

confidence: 99%

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Implications of the Colonic Deposition of Free Hemoglobin-α Chain

Myers

Schaffer

Korolkova

et al. 2014

Inflammatory Bowel Diseases

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Purpose We analyzed inflamed mucosal/submucosal layers of ulcerative colitis (UC=63) and Crohn’s colitis (CC=50) and unexpectedly we unveiled a pool of free-hemoglobin-alpha (Hb-α) chain. Patients with colitides have increased ROS, DNA-oxidation products, free-iron in mucosa, in pre-neoplastic, and in colitis-cancers and increased risks of developing colorectal-cancer (CRC). All IBD-related-CRC lesions are found in segments with colitis. Linking this information we investigated whether free-Hb-α is key transformational stepping that increases colitis-related-CRC vulnerability. Methods UC/CC samples were profiled using MALDI-MS; protein identification was made by LCM. Diverticulitis (DV) was used as control (Ctrl). The presence of Hb(n) (n=α, β and hemin)/Hb was validated by Western blotting (WB) and immunohistochemistry (IHC). We tested for DNA-damage (DNAD) by exposing normal colonic-epithelial-cell-line, NCM460, to 10μM and 100μM of Hb(n)/Hb, individually for 2 h, 6 h, and 12 h. Quantification of Hb-α-staining was done by Nikon Elements Advance Research Analysis software. ROS was measured by the production of 8-OHdG. DNAD was assessed by Comet-assay. Colonic tissue homogenate antioxidants Nrf2-, CAT-, SOD- and GPx-expressions was analyzed densitometrically/ normalized by β-actin. Results IHC of CC/UC mucosal/submucosal-compartments stained strongly positive for Hb-α and significantly higher vs. Ctrl. NCM460 exposed to Hb(n)/Hb exhibited steadily-increasing ROS and subsequent DNAD. DNAD was higher in 10μM than 100μM in Hb-β/hemin the first 2 h then plateaued followed by DNAD-repair. This may be likely due to apoptosis in the later concentration. Nrf2 enzyme activities among UC, CC and UCAC were observed impaired in all IBD subjects. Decreased levels of Nrf2 among UC vs. CC patients with active disease was insignificant as well as vs. Ctrls but significantly lower in UCAC vs. Ctrl. SOD was decreased in UC and UCAC and GPx in CC but statistically not significant. Comparing CC vs. UC, SOD was significantly lower in CC (p< 0.05). CAT was observed increased among CC/UC/UCAC patients and GPx in UC and UCAC vs. Ctrl, respectively, and significantly increased in CC vs. Ctrl (p< 0.01) Conclusion In the colitides mucosal/submucosal tissue microenvironments demonstrated pool of free-Hb-α-chain. In vitro exposure of NCM460-cells to Hb(n)/Hb induced ROS and DNAD. Toxic effect of free-Hb-α, in colonic epithelial cells is therefore through production of ROS-formation modulated by impairment of antioxidant effects. Targeting reduction-oxidation-sensitive pathways and transcription factors may offer options for IBD-management and colitis-related-cancer prevention.

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“…While we did not include healthy controls in this investigation, the values of BAP in our patients were generally low, with more than half of the patients having values less than 2200 μmol/L. In previous studies, a reduction in serum antioxidant capacity was found in patients with inflammatory bowel disease (IBD) [17,27,28] . On the other hand, evidence for enhancement of antioxidant capacity was also found in biopsy specimens from IBD patients [19] .…”

Section: Discussionmentioning

confidence: 99%

Effect of tumor necrosis factor-α antagonists on oxidative stress in patients with Crohn’s disease

Yamamoto

Chiba

Matsumoto

2015

WJG

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AIM:To investigate changes in oxidative stress in Crohn's disease (CD) before and after anti-tumor necrosis factor (TNF)-α treatment. METHODS:A total of 42 patients with active CD, who were scheduled to be treated by anti-TNF-α antibodies, were enrolled. Serum levels of diacron-reactive oxygen metabolites (d-ROM), biological antioxidant potential (BAP), and modified ratio of oxidative stress and antioxidant capacity (m-OA) were measured using the Free Radical Analytical System before and 8 wk after induction of therapy with infliximab or adalimumab. The values for oxidative stress were correlated with disease activity and clinical response as determined by the CD activity index (CDAI) at 8 and 54 wk after the therapy. RESULTS:Prior to treatment, d-ROM showed significant correlations with CDAI (r = 0.42, P < 0.01).There was a significant negative correlation between m-OA and CDAI before and after treatment (r = -0.48 vs r = -0.42, P < 0.01). CDAI and d-ROM had decreased significantly by 8 wk after treatment (CDAI; 223.3 ± 113.2 vs 158.3 ± 73.4, P < 0.01, d-ROM; 373 ± 133 vs 312 ± 101, P < 0.05). However, neither BAP nor m-OA had changed significantly. In patients who had responded to the treatment at 8 wk, d-ROM, BAP, and m-OA levels before treatment did not differ significantly between patients with and without loss of response. CONCLUSION: Anti-TNF-α therapy decreases oxi- Clinical Trials Study

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

Cited by 160 publications

References 25 publications

Decreased Total Antioxidant Capacity in Plasma, but Not Tissue, in Experimental Colitis

Decreased Total Antioxidant Capacity in Plasma, but Not Tissue, in Experimental Colitis

Implications of the Colonic Deposition of Free Hemoglobin-α Chain

Effect of tumor necrosis factor-α antagonists on oxidative stress in patients with Crohn’s disease

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