Monzo-Beltran Lidia, Vazquez-Tarragón Antonio, Cerdà Concha, Garcia-Perez Paula, Iradi Antonio, Sánchez Carlos, Climent Benjamin, Tormos Carmen, Vázquez-Prado Antonio, Girbés Javier, Estáñ Nuria, Blesa Sebastián, Cortés Raquel, Chaves Felipe J, Sáez Guillermo T
Dept. of Biochemistry and Molecular Biology, Faculty of Medicine and Odontology-INCLIVA, University of Valencia, Spain.
Service of General and Digestive Surgery, University Hospital Dr. Peset, Valencia, Spain.
Redox Biol. 2017 Aug;12:389-402. doi: 10.1016/j.redox.2017.02.003. Epub 2017 Feb 14.
Obesity has grown worldwide over the last few decades. In its different degrees, obesity is accompanied by many clinical and biochemical alterations reflecting the pathological condition of various body tissues. Among the mechanisms underlying the pathogenesis of obesity and associated complications, oxidative stress (OS) may be playing an important role. In the present study, we have characterized at systemic level the degree of OS status in a group of morbid obese patients (BMI>40kg/m) at basal sate and its modulation during one year after bariatric surgery using the laparoscopic sleeve gastrectomy (LSG) technique. As compared with normal weight subjects matched in age, peripheral blood mononuclear cells (PBMc) of obese patients present a significant reduction of the antioxidant enzyme activities superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) as well as a significant increase of the oxidized/reduced glutathione ratio (GSSG/GSH) in these cells. Lipid peroxidation is significantly increased in the patient group as shown by the increased levels of malondialdehyde (MDA) in PBMc and the amount of F2-Isoprostanes (F2-IsoPs) released in urine. In addition, the DNA damage product 8-oxo-7,8-2'-deoxyguanosine (8-oxo-dG) was also observed to be increased in serum and urine of morbid obese patients as compared with the control group. After LSG, an improvement of their ponderal and metabolic profile was accompanied by a progressive recovery of antioxidant enzyme activities and the decline of oxidative byproducts both in PBMc and biological fluids. The observed changes of urinary 8-oxo-dG levels correlate positively with its serum concentration, the lipid peroxidation products MDA and F2-IsoPs, triglycerides, glucose, insulin, HOMA index and body weight and negatively with the percentage of weight and BMI loss and antioxidant activities. We conclude that the analysis of urinary 8-oxo-dG could be validated as a useful marker for the monitoring of ponderal and metabolic status of morbid obese patients.
在过去几十年间，肥胖在全球范围内呈增长态势。肥胖在不同程度上伴随着许多临床和生化改变，这些改变反映了身体各组织的病理状况。在肥胖及其相关并发症发病机制的潜在机制中，氧化应激（OS）可能起着重要作用。在本研究中，我们在系统水平上对一组病态肥胖患者（BMI>40kg/m²）在基础状态下的氧化应激状态程度及其在采用腹腔镜袖状胃切除术（LSG）技术进行减肥手术后一年中的变化情况进行了表征。与年龄匹配的正常体重受试者相比，肥胖患者的外周血单核细胞（PBMC）中抗氧化酶超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPx）的活性显著降低，并且这些细胞中的氧化型/还原型谷胱甘肽比率（GSSG/GSH）显著升高。患者组中的脂质过氧化显著增加，这通过PBMC中丙二醛（MDA）水平的升高以及尿液中释放的F2-异前列腺素（F2-IsoPs）量得以体现。此外，与对照组相比，病态肥胖患者的血清和尿液中的DNA损伤产物8-氧代-7,8-二氢-2'-脱氧鸟苷（8-氧代-dG）也被观察到有所增加。在LSG手术后，他们的体重和代谢状况得到改善，同时PBMC和生物体液中的抗氧化酶活性逐渐恢复，氧化副产物减少。观察到的尿8-氧代-dG水平变化与其血清浓度、脂质过氧化产物MDA和F2-IsoPs、甘油三酯、葡萄糖、胰岛素、HOMA指数及体重呈正相关，与体重和BMI下降百分比及抗氧化活性呈负相关。我们得出结论，尿8-氧代-dG分析可被确认为监测病态肥胖患者体重和代谢状况的有用标志物。
