Luceri Cristina, Bigagli Elisabetta, Agostiniani Sara, Giudici Francesco, Zambonin Daniela, Scaringi Stefano, Ficari Ferdinando, Lodovici Maura, Malentacchi Cecilia
Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology, University of Florence, 50139 Florence, Italy.
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy.
Antioxidants (Basel). 2019 Sep 6;8(9):378. doi: 10.3390/antiox8090378.
Crohn' disease (CD) patients are at high risk of postoperative recurrence and new tools for the assessment of disease activity are needed to prevent long-term complications. In these patients, the over-production of ROS generated by inflamed bowel tissue and inflammatory cells activates a pathogenic cascade that further exacerbates inflammation and leads to increased oxidative damage to DNA, proteins, and lipids. We measured the products of protein/lipid oxidation and the total antioxidant capacity (ferric reducing ability of plasma, FRAP) in the serum of CD patients with severe disease activity requiring surgery with the aim to characterize their redox status and identify associations between oxidative stress-related markers and their clinical characteristics. At the systemic level, CD was associated with increased levels of protein and lipid oxidation products when compared to healthy volunteers, even though the FRAP values were similar. Advanced oxidation protein product (AOPP) levels showed the highest difference between patients and the controls (11.25, 5.02-15.15, vs. 1.36, 0.75-2.70, median, interquartile range; < 0.0001) and the analysis of receiver operating characteristic (ROC) curves, indicated for AOPP, the best area under the curve (AUC) value for CD prediction. Advanced glycated end-products (AGEs) were also significantly higher in CD patients ( < 0.01), which is of interest since AOPP and AGEs are both able to activate the membrane receptor for advanced glycation end products (RAGE) involved in inflammatory diseases. Thiobarbituric acid reactive substance (TBARS) levels were significantly higher in CD patients with ileal localization and aggressive disease behavior, in smokers, and in patients suffering from allergies. In conclusion, our data indicate that circulating oxidative stress biomarkers may be attractive candidates as disease predictors as well as for clinical or therapeutic monitoring of CD. Our results also suggest that AOPP/AGEs and RAGE signaling may represent a pathogenic factor and a potential therapeutic target in CD.
克罗恩病（CD）患者术后复发风险很高，因此需要新的疾病活动评估工具来预防长期并发症。在这些患者中，炎症性肠组织和炎症细胞产生的活性氧（ROS）过度生成会激活致病级联反应，进一步加剧炎症，并导致DNA、蛋白质和脂质的氧化损伤增加。我们测量了患有严重疾病活动且需要手术的CD患者血清中蛋白质/脂质氧化产物和总抗氧化能力（血浆铁还原能力，FRAP），旨在表征他们的氧化还原状态，并确定氧化应激相关标志物与其临床特征之间的关联。在系统水平上，与健康志愿者相比，CD患者的蛋白质和脂质氧化产物水平升高，尽管FRAP值相似。晚期氧化蛋白产物（AOPP）水平在患者和对照组之间显示出最大差异（中位数，四分位间距：11.25，5.02 - 15.15， vs. 1.36，0.75 - 2.70；<0.0001），并且对接受者操作特征（ROC）曲线的分析表明，AOPP对CD预测的曲线下面积（AUC）值最佳。晚期糖基化终产物（AGEs）在CD患者中也显著更高（<0.01），这很有意思，因为AOPP和AGEs都能够激活参与炎症性疾病的晚期糖基化终产物膜受体（RAGE）。硫代巴比妥酸反应性物质（TBARS）水平在回肠定位、侵袭性疾病行为的CD患者、吸烟者以及患有过敏症的患者中显著更高。总之，我们的数据表明，循环氧化应激生物标志物可能是作为疾病预测指标以及CD临床或治疗监测的有吸引力的候选物。我们的结果还表明，AOPP/AGEs和RAGE信号传导可能代表CD中的致病因素和潜在治疗靶点。
