Elevated urinary levels of 8-oxo-2′-deoxyguanosine, (5′R)- and (5′S)-8,5′-cyclo-2′-deoxyadenosines, and 8-iso-prostaglandi F2α as potential biomarkers of oxidative stress in patients with prediabetes

被引:34
|
作者
Kant, Melis [1 ]
Akis, Merve [1 ]
Calan, Mehmet [2 ]
Arkan, Tugba [3 ]
Bayraktar, Firat [4 ]
Dizdaroglu, Miral [5 ]
Islekel, Huray [1 ,6 ]
机构
[1] Dokuz Eylul Univ, Sch Med, Inst Hlth Sci, Dept Med Biochem, TR-35340 Izmir, Turkey
[2] Izmir Bozkaya Res & Educ Hosp, Div Endocrinol, TR-35170 Izmir, Turkey
[3] Derince Res & Educ Hosp, Div Endocrinol, TR-41900 Kocaeli, Turkey
[4] Dokuz Eylul Univ, Sch Med, Div Endocrinol & Metab, Dept Internal Med, TR-35340 Izmir, Turkey
[5] NIST, Biomol Measurement Div, Gaithersburg, MD 20899 USA
[6] Dokuz Eylul Univ, Inst Hlth Sci, Sch Med, Dept Mol Med, TR-35340 Izmir, Turkey
关键词
Oxidatively induced DNA damage; Lipid peroxidation; Prediabetes; 8-Oxo-2 '-deoxyguanosine; 8,5 '-cyc/o-2 '-Deoxyadenosines; 8-iso-Prostaglandin F-2 alpha; EXCISION-REPAIR PATHWAY; MODIFIED DNA LESIONS; MASS-SPECTROMETRY; DAMAGE; MECHANISMS; MARKERS; 8-OXO-7,8-DIHYDRO-2'-DEOXYGUANOSINE; 8-OXO-7,8-DIHYDROGUANINE; QUANTIFICATION; IDENTIFICATION;
D O I
10.1016/j.dnarep.2016.09.004
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Prediabetes is the preclinical stage of type 2 diabetes mellitus (T2DM) with intermediate state of hyperglycemia. Hyperglycemia results in a state of oxidative stress, which may contribute to the production of insulin resistance, beta-cell dysfunction and long-term complications of diabetes. Novel approaches are required for prevention and treatment of diabetes. New biomarkers that can be used in risk stratification and therapy control as supplementary'to current parameters are needed. These biomarkers may facilitate a more individualized and sufficient treatment of diabetes. Therefore, the aim of this study was to investigate the levels of oxidatively induced DNA damage products, 8-oxo-2'-deoxyguanosine (8-oxo-dG) (also known as 8-OH-dG), (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines (R-cdA and S-cdA), and the lipid peroxidation product 8-iso-prostaglandin F-2 alpha, (8-iso-PGF(2 alpha)) as reliable oxidative stress markers in patients with prediabetes or T2DM in comparison with healthy volunteers. Urine samples were collected from these subjects. Absolute quantification of 8-oxo-dG, R-cdA, S-cdA and 8-iso-PGF(2 alpha) was achieved by liquid chromatography-isotope dilution tandem mass spectrometry. The levels of 8-oxo-dG, S-cdA and 8-iso-PGF(2 alpha) were significantly greater in prediabetes patients than those in healthy volunteers. T2DM patients also had higher levels of 8-oxo-dG than healthy volunteers. No statistically significant difference was observed for R-cdA levels. 8-Oxo-dG levels positively correlated with R-cdA and S-cdA levels for prediabetes and newly diagnosed T2DM. S-cdA levels and HbAlc were found negatively correlated in prediabetes patients. Also 8-iso-PGF(2 alpha) levels and HbAlc were found negatively correlated in prediabetes patients. These results indicate that oxidatively induced macromolecular damage appears before the establishment of T2DM. Thus, our data suggest that oxidatively induced DNA damage and lipid peroxidation products that were found to be elevated in prediabetic stage may be used as early disease markers in patients at risk for T2DM. (C) 2016 Elsevier B.V. All rights reserved.
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页码:1 / 7
页数:7
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