Pereira Cristiana, Coelho Rosa, Grácio Daniela, Dias Cláudia, Silva Marco, Peixoto Armando, Lopes Pedro, Costa Carla, Teixeira João Paulo, Macedo Guilherme, Magro Fernando
National Institute of Health - Environmental Health Department, Oporto, Portugal.
MedInUP - Centre for Drug Discovery and Innovative Medicines, University of Oporto, Oporto, Portugal.
J Crohns Colitis. 2016 Nov;10(11):1316-1323. doi: 10.1093/ecco-jcc/jjw088. Epub 2016 Apr 19.
Inflammation has long been regarded as a major contributor to cellular oxidative damage and to be involved in the promotion of carcinogenesis.
We aimed to investigate the oxidative damage in inflammatory bowel disease [IBD] patients through a case-control and prospective study involving 344 IBD patients and 294 healthy controls. DNA damage and oxidative DNA damage were measured by comet assay techniques, and oxidative stress by plasmatic lipid peroxidation, protein carbonyls, and total antioxidant capacity.
Higher DNA damage [p < 0.001] was found both in Crohn's disease [CD] (9.7 arbitrary units [AU]; interquartile range [IQR]: 6.2-14.0) and ulcerative colitis [UC] [7.1 AU; IQR: 4.4-11.7], when compared with controls [5.4 AU; IQR: 3.8-6.8], and this was also the case with oxidative DNA damage [p < 0.001] [CD: 3.6 AU; IQR: 1.8-6.8; UC: 4.6 AU; IQR: 2.4-8.1], when compared with controls: 2.3 AU; IQR: 1.2-4.2]. Stratifying patients into groups according to therapy (5-aminosalicylic acid [5-ASA], azathioprine, anti-TNF, and combined therapy [azathioprine and anti-TNF]) revealed significant between-group differences in the level of DNA damage, both in CD and UC, with the combined therapy exhibiting the highest DNA damage levels [11.6 AU; IQR: 9.5-14.3, and 12.4 AU; IQR: 10.6-15.0, respectively]. Among CD patients, disease behaviour [B1 and B2], and age at diagnosis over 40 years [A3] stand as risk factors for DNA damage. For UC patients, the risk factors found for DNA damage were disease activity, treatment, age at diagnosis under 40 years [A1 + A2] and disease locations [E2 and E3].
In IBD there is an increase in DNA damage, and treatment, age at diagnosis and inflammatory burden seem to be risk factors.
长期以来，炎症一直被视为细胞氧化损伤的主要促成因素，并参与致癌作用。
我们旨在通过一项病例对照和前瞻性研究，对344例炎症性肠病（IBD）患者和294例健康对照者进行调查，以研究IBD患者的氧化损伤情况。采用彗星试验技术检测DNA损伤和氧化性DNA损伤，通过血浆脂质过氧化、蛋白质羰基化和总抗氧化能力检测氧化应激。
与对照组[5.4任意单位（AU）；四分位间距（IQR）：3.8 - 6.8]相比，克罗恩病（CD）（9.7 AU；IQR：6.2 - 14.0）和溃疡性结肠炎（UC）[7.1 AU；IQR：4.4 - 11.7]患者的DNA损伤均更高（p < 0.001），氧化性DNA损伤情况也是如此（p < 0.001）[CD：3.6 AU；IQR：1.8 - 6.8；UC：4.6 AU；IQR：2.4 - 8.1]，而对照组为2.3 AU；IQR：1.2 - 4.2]。根据治疗方法（5 - 氨基水杨酸[5 - ASA]、硫唑嘌呤、抗TNF以及联合治疗[硫唑嘌呤和抗TNF]）将患者分组后发现，CD和UC患者中，DNA损伤水平在组间存在显著差异，联合治疗组的DNA损伤水平最高[分别为11.6 AU；IQR：9.5 - 14.3和12.4 AU；IQR：10.6 - 15.0]。在CD患者中，疾病行为[B1和B2]以及诊断时年龄超过40岁[A3]是DNA损伤的危险因素。对于UC患者，发现DNA损伤的危险因素包括疾病活动度、治疗、诊断时年龄小于40岁[A1 + A2]以及疾病部位[E2和E3]。
在IBD中，DNA损伤增加，治疗、诊断时年龄和炎症负担似乎是危险因素。
