Department of Gastroenterology, Hospital Universitari La Fe, Valencia, Spain.
Inflamm Bowel Dis. 2010 Jan;16(1):76-86. doi: 10.1002/ibd.21027.
Oxidative stress is considered a potential etiological factor for Crohn's disease (CD). We characterized the reactive oxygen species (ROS) generated in immune peripheral cells of CD patients, as well as their antioxidant enzyme status and the presence of oxidative damage. In addition, mitochondrial function (DeltaPsim) was analyzed to detect the possible origin of ROS.
Cells were obtained from patients at the onset of disease, prior to any treatment. Experiments were repeated when patients were in clinical remission. A set of experiments was carried out in a group of CD patients in persistent morphological remission. Controls were healthy volunteers who were not receiving any treatment at the time. The generation of superoxide, hydrogen peroxide (H(2)O(2)) and nitric oxide, DeltaPsim, superoxide dismutase (SOD) and catalase (CAT) activities, and concentrations of malondyaldehyde (MDA) and 8-oxo-deoxyguanosine (8-oxo-dG) were measured.
SOD activity and H(2)O(2) production were significantly higher during active CD but returned to control levels in remission. DeltaPsim was inhibited during active CD and, although it returned to control levels, its recovery took longer than clinical remission. CAT activity was permanently inhibited during CD, independent of the disease activity. MDA and 8-oxo-dG were permanently elevated.
Oxidative stress during active CD depends on H(2)O(2) production. The inhibition of DeltaPsim suggests that this organelle is a source of ROS. CAT is permanently inhibited in CD, the biological significance of which is under study. The persistent oxidative damage detected may have implications for the evolution of the disease.
氧化应激被认为是克罗恩病（CD）的潜在病因。我们对 CD 患者免疫外周细胞中产生的活性氧（ROS）、抗氧化酶状态以及氧化损伤的存在进行了特征分析。此外，还分析了线粒体功能（ΔΨm）以检测 ROS 的可能来源。
在开始治疗之前，从患者疾病发作时获得细胞。当患者处于临床缓解期时，重复进行实验。在一组持续形态缓解的 CD 患者中进行了一组实验。对照组为当时未接受任何治疗的健康志愿者。测量了超氧化物、过氧化氢（H₂O₂）和一氧化氮的生成、ΔΨm、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性，以及丙二醛（MDA）和 8-氧代脱氧鸟苷（8-oxo-dG）的浓度。
SOD 活性和 H₂O₂的产生在活动期 CD 时明显升高，但在缓解期恢复到对照水平。ΔΨm 在活动期 CD 时受到抑制，尽管它恢复到对照水平，但恢复时间长于临床缓解期。CAT 活性在 CD 期间持续受到抑制，与疾病活动无关。MDA 和 8-oxo-dG 持续升高。
活动期 CD 中的氧化应激取决于 H₂O₂的产生。ΔΨm 的抑制表明该细胞器是 ROS 的来源。CAT 在 CD 中持续受到抑制，其生物学意义正在研究中。持续存在的氧化损伤可能对疾病的演变有影响。
