Oxidative Stress, DNA Damage and DNA Repair in Female Patients with Diabetes Mellitus Type 2

被引:52
作者
Grindel, Annemarie [1 ,2 ]
Guggenberger, Bianca [1 ]
Eichberger, Lukas [1 ]
Poeppelmeyer, Christina [1 ]
Gschaider, Michaela [1 ]
Tosevska, Anela [1 ]
Mare, George [1 ]
Briskey, David [3 ]
Brath, Helmut [4 ]
Wagner, Karl-Heinz [1 ,2 ]
机构
[1] Univ Vienna, Dept Nutr Sci Emerging Field Oxidat Stress & DNA, Vienna, Austria
[2] Univ Vienna, Res Platform Act Ageing, Vienna, Austria
[3] Univ Queensland, Sch Human Movement & Nutr Sci, St Lucia, Qld, Australia
[4] Hlth Ctr South, Diabet Outpatient Clin, Vienna, Austria
关键词
BETA-CELL FAILURE; INSULIN-RESISTANCE; GLYCEMIC CONTROL; COMET ASSAY; GLUTATHIONE; ASSOCIATION; BASE; QUANTIFICATION; COMPLICATIONS; PATHOGENESIS;
D O I
10.1371/journal.pone.0162082
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Background Diabetes mellitus type 2 (T2DM) is associated with oxidative stress which in turn can lead to DNA damage. The aim of the present study was to analyze oxidative stress, DNA damage and DNA repair in regard to hyperglycemic state and diabetes duration. Methods Female T2DM patients (n = 146) were enrolled in the MIKRODIAB study and allocated in two groups regarding their glycated hemoglobin (HbA1c) level (HbA1c <= 7.5%, n = 74; HbA1c> 7.5%, n = 72). In addition, tertiles according to diabetes duration (DD) were created (DDI = 6.94 +/- 3.1 y, n = 49; DDII = 13.35 +/- 1.1 y, n = 48; DDIII = 22.90 +/- 7.3 y, n = 49). Oxidative stress parameters, including ferric reducing ability potential, malondialdehyde, oxidized and reduced glutathione, reduced thiols, oxidized LDL and F2-Isoprostane as well as the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were measured. Damage to DNA was analyzed in peripheral blood mononuclear cells and whole blood with single cell gel electrophoresis. DNA base excision repair capacity was tested with the modified comet repair assay. Additionally, mRNA expressions of nine genes related to base excision repair were analyzed in a subset of 46 matched individuals. Results No significant differences in oxidative stress parameters, antioxidant enzyme activities, damage to DNA and base excision repair capacity, neither between a HbA1c cut off /> 7.5%, nor between diabetes duration was found. A significant up-regulation in mRNA expression was found for APEX1, LIG3 and XRCC1 in patients with > 7.5% HbA1c. Additionally, we observed higher total cholesterol, LDL-cholesterol, LDL/HDL-cholesterol, triglycerides,Framingham risk score, systolic blood pressure, BMI and lower HDL-cholesterol in the hyperglycemic group. Conclusion BMI, blood pressure and blood lipid status were worse in hyperglycemic individuals. However, no major disparities regarding oxidative stress, damage to DNA and DNA repair were present which might be due to good medical treatment with regular health checks in T2DM patients in Austria.
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页数:17
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