DNA damage, oxidative stress, and inflammation in children with celiac disease

Abstract The objective of this study was to evaluate the level of genomic instability in patients with celiac disease and to establish a relationship between inflammation, oxidative stress, and DNA damage in these patients. Myeloperoxidase (MPO) activity, adenosine deaminase, nitric oxide (NOx), thiobarbituric acid, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and DNA damage were evaluated in peripheral blood samples from 47 celiac disease patients and 31 controls. Patients with celiac disease presented higher levels of DNA damage in comparison to controls (p=0.023). This difference was also observed for markers of oxidative stress, such as CAT (p=0.011) and SOD (p=0.013), and inflammatory markers such as MPO (p < 0.001) and NOx (p=0.009). Positive correlations were found between DNA damage levels and the values of CAT (r=0.405; p=0.009) and SOD (r=0.516; p < 0.001). Positive correlations were also found between GPx and NOx (r=0.349; p=0.030) and MPO and NOx (r=0.239; p=0.039). CAT and NOx showed a negative correlation (r= −0.315; p=0.042). In conclusion, intestinal inflammation can have systemic effects, causing an imbalance between oxidant and antioxidant markers, which may promote increased levels of DNA damage.

摘要 本研究旨在评估乳糜泻 (celiac disease) 患者的基因组不稳定水平，并明确此类患者体内炎症、氧化应激与DNA损伤之间的关联。研究对47例乳糜泻患者与31名健康对照的外周血样本开展检测，检测指标包括髓过氧化物酶 (Myeloperoxidase, MPO) 活性、腺苷脱氨酶、一氧化氮 (nitric oxide, NOx)、硫代巴比妥酸、过氧化氢酶 (catalase, CAT)、超氧化物歧化酶 (superoxide dismutase, SOD)、谷胱甘肽过氧化物酶 (glutathione peroxidase, GPx) 水平以及DNA损伤程度。相较于健康对照组，乳糜泻患者的DNA损伤水平显著升高（p=0.023）。该差异在氧化应激标志物（如CAT (p=0.011) 与SOD (p=0.013)）及炎症标志物（如MPO (p < 0.001) 与NOx (p=0.009)）中均有体现。研究发现，DNA损伤水平与CAT (r=0.405; p=0.009)、SOD (r=0.516; p < 0.001) 的检测值呈正相关；GPx与NOx (r=0.349; p=0.030)、MPO与NOx (r=0.239; p=0.039) 亦呈正相关；而CAT与NOx则呈负相关 (r= −0.315; p=0.042)。综上，肠道炎症可产生全身性效应，引发氧化与抗氧化标志物失衡，进而可能促进DNA损伤水平升高。