DNA Damage and Oxidative DNA Damage in Inflammatory Bowel Disease

Pereira, Cristiana; Coelho, Rosa; Grácio, Daniela; Dias, Cláudia Camila; Silva, Marco; Peixoto, Armando; Lopes, P; Costa, Carla; Teixeira, João Paulo; Macedo, Guilherme; Magro, Fernando

doi:10.1093/ecco-jcc/jjw088

Cited by 83 publications

(84 citation statements)

References 39 publications

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“…DNA damage is largely linked to ROS production in inflammatory conditions, including IBD . The protective effect of antioxidant molecules via a decrease in oxidative damage to DNA has been shown in various models .…”

Section: Resultscontrasting

confidence: 62%

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Mannino

Caradonna

Cruciata

et al. 2019

Journal of Pineal Research

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Melatonin is the main secretory product of the pineal gland, and it is involved in the regulation of periodic events. A melatonin production independent of the photoperiod is typical of the gut. However, the local physiological role of melatonin at the intestinal tract is poorly characterized. In this study, we evaluated the anti‐inflammatory activities of melatonin in an in vitro model of inflamed intestinal epithelium. To this purpose, we assessed different parameters usually associated with intestinal inflammation using IL‐1β‐stimulated Caco‐2 cells. Differentiated monolayers of Caco‐2 cells were preincubated with melatonin (1 nmol/L‐50 μmol/L) and then exposed to IL‐1β. After each treatment, different inflammatory mediators, DNA‐breakage, and global DNA methylation status were assayed. To evaluate the involvement of melatonin membrane receptors, we also exposed differentiated monolayers to melatonin in the presence of luzindole, a MT1 and MT2 antagonist. Our results showed that melatonin, at concentrations similar to those obtained in the lumen gut after ingestion of dietary supplements for the treatment of sleep disorders, was able to attenuate the inflammatory response induced by IL‐1β. Anti‐inflammatory effects were expressed as both a decrease of the levels of inflammatory mediators, including IL‐6, IL‐8, COX‐2, and NO, and a reduced increase in paracellular permeability. Moreover, the protection was associated with a reduced NF‐κB activation and a prevention of DNA demethylation. Conversely, luzindole did not reverse the melatonin inhibition of stimulated‐IL‐6 release. In conclusion, our findings suggest that melatonin, through a local action, can modulate inflammatory processes at the intestinal level, offering new opportunities for a multimodal management of IBD.

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Section: Resultscontrasting

confidence: 62%

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Mannino

Caradonna

Cruciata

et al. 2019

Journal of Pineal Research

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“…OS‐induced damage to DNA also contributes to neurodegeneration, promoting Parkinson's disease, Alzheimer's disease, and sporadic amyotrophic lateral sclerosis . Other health disorders arising from oxidative damage to DNA are cardiovascular diseases, Wilson's disease, Huntington's disease, inflammatory bowel disease, acquired immunodeficiency syndrome, diabetes and its complications, chronic obstructive pulmonary disease, and rheumatoid arthritis …”

Section: Introductionmentioning

confidence: 99%

Melatonin and its metabolites as chemical agents capable of directly repairing oxidized DNA

Pérez-González

Castañeda‐Arriaga

Álvarez-Idaboy

et al. 2018

Journal of Pineal Research

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Oxidative stress mediates chemical damage to DNA yielding a wide variety of products. In this work, the potential capability of melatonin and several of its metabolites to repair directly (chemically) oxidative lesions in DNA was explored. It was found that all the investigated molecules are capable of repairing guanine‐centered radical cations by electron transfer at very high rates, that is, diffusion‐limited. They are also capable of repairing C‐centered radicals in the sugar moiety of 2′‐deoxyguanosine (2dG) by hydrogen atom transfer. Although this was identified as a rather slow process, with rate constants ranging from 1.75 to 5.32 × 102 M−1 s−1, it is expected to be fast enough to prevent propagation of the DNA damage. Melatonin metabolites 6‐hydroxymelatonin (6OHM) and 4‐hydroxymelatonin (4OHM) are also predicted to repair OH adducts in the imidazole ring. In particular, the rate constants corresponding to the repair of 8‐OH‐G adducts were found to be in the order of 104 M−1 s−1 and are assisted by a water molecule. The results presented here strongly suggest that the role of melatonin in preventing DNA damage might be mediated by its capability, combined with that of its metabolites, to directly repair oxidized sites in DNA through different chemical routes.

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“…Intracolonic instillation of AA as a dilute solution produces an acute and non‐transmural colonic inflammation that is qualified with elevated leukocyte infiltration into the bowel tissue, overproduction of inflammatory mediators, vascular dilatation, edema, and large necrosis of mucosal and submucosal layers following submucosal ulceration as in UC . Oxidative stress appears to be the essential pathogenic determinant in UC, because of the elevated reactive oxygen species (ROS) (superoxide anion, hydrogen peroxide, hypochlorite and hydroxyl radical and nitrogen species) levels in patients . Compatibly, an imbalance between oxidant and antioxidant substances is the characteristic feature of AA‐induced experimental UC in animals …”

Section: Introductionmentioning

confidence: 99%

Ameliorative effects of riboflavin on acetic acid‐induced colonic injury in rats

Karakoyun

Ertaş

Yüksel

et al. 2017

Clin Exp Pharma Physio

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Riboflavin (RF) has been found to be a promising antioxidant and/or anti-inflammatory agent in several studies. However, the effect of RF against acetic acid (AA)-induced colonic injury is currently unknown. This study aimed to investigate the potential antioxidant and protective effects of RF in a rat model of ulcerative colitis. Starting immediately after the colitis induction (AA+RF group) or 1 week before the colitis induction (RF+AA+RF group), the rats were treated with RF (25 mg/kg per day; p.o.) for 3 days. The control and AA groups received saline (1 mL; p.o.) whereas AA+SS group (positive control) received sulfasalazine (100 mg/kg per day; p.o.) for 3 days. Colonic samples were taken for the biochemical and histological assessments on the third day. High damage scores, elevated tissue wet weight index (WI), tissue myeloperoxidase (MPO) activity, 8-hydroxy-2'-deoxyguanosine levels and chemiluminescence values, and a pronounced decrease in antioxidant glutathione (GSH) levels of the AA group were all reversed by RF pretreatment (RF+AA+RF group) and SS treatment (AA+SS group) (P < .05-.001). Tissue WI, MPO activity and GSH levels were not statistically changed in the AA+RF group. Western blot analysis revealed that the decreased protein expressions of tissue collagen (COL) 1A1, COL3A1 and transforming growth factor-β1 in the AA group were elevated in all the treatment groups (P < .05-.001). In conclusion, RF exerts both the antioxidant and anti-inflammatory effects against AA-induced colonic inflammation by suppressing neutrophil accumulation, inhibiting reactive oxidant generation, preserving endogenous glutathione, improving oxidative DNA damage and regulating inflammatory mediators, suggesting a future potential role in the treatment and prevention of ulcerative colitis.

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DNA Damage and Oxidative DNA Damage in Inflammatory Bowel Disease

Abstract: In IBD there is an increase in DNA damage, and treatment, age at diagnosis and inflammatory burden seem to be risk factors.

Cited by 83 publications

References 39 publications

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Melatonin and its metabolites as chemical agents capable of directly repairing oxidized DNA

Ameliorative effects of riboflavin on acetic acid‐induced colonic injury in rats

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