Cholesterol oxides as biomarkers of oxidative stress in type 1 and type 2 diabetes mellitus
Cholesterol oxides as biomarkers of oxidative stress in type 1 and type 2 diabetes mellitus
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DOI：
10.1002/dmrr.645
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发表时间：
2007-01-01
影响因子：
8
通讯作者：
Abdalla, D. S. P.
中科院分区：
文献类型：
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作者：
Ferderbar, S.;Pereira, E. C.;Abdalla, D. S. P.
背景氧化应激在糖尿病的病理生理学中起着重要作用。本研究的目的是评估胆固醇氧化物（ChOx）的形成，作为糖耐量受损（IGT）和糖尿病受试者氧化应激的生物标志物。方法测定以下组中胆固醇氧化产物的血浆水平：I型糖尿病（DM1）、2型糖尿病（DM2）、糖耐量受损（IGT）、无糖尿病儿童（C1）和无糖尿病成人（C2）。 cholest-5-ene-3 α,7 α-二醇（7 α-羟基胆固醇，7 α-OH）、cholest-5-ene-3 β,7 β-二醇（7 β-羟基胆固醇，7 β-OH）、3 β-羟基胆固醇-5-7-一（7-酮胆固醇，7-K）、5 α-胆甾烷-3 β,5,6的血清水平β-三醇（胆甾烷三醇）、5,6 α-环氧-5 α-胆甾烷-3 α-醇（胆固醇5 α, 6 α-环氧化物）、5,6 β-环氧-5 β-胆甾烷-3 β-醇（胆固醇-5 β,6 β-环氧化物）和 cholest-5-eno-3 β,25-二醇（25-羟基胆固醇， 25-OH）（括号中所示的俗名和缩写）通过使用火焰离子化检测的气相色谱法进行定量。 结果 与年龄匹配的非糖尿病受试者相比，DM1 和 DM2 组的总 ChOx 水平升高（p < 0.05）。 DM2组受试者血浆中7β-羟基胆固醇、胆固醇-α-环氧化物和胆固醇-β-环氧化物的浓度高于C2和IGT组受试者血浆中的浓度(p < 0.05)。使用与胰岛素相关的口服降糖药物治疗2型糖尿病患者可降低血浆中硝基酪氨酸的浓度，而葡萄糖和糖化血红蛋白的浓度没有显着变化。此外，与他汀类药物联合使用，两种治疗均降低了 ChOx 的浓度。结论 ChOx 是氧化应激的合适生物标志物，可用于临床研究，以跟踪药物对糖尿病患者脂质氧化修饰的影响。版权所有 (c) 2006 John Wiley & Sons, Ltd.
Background Oxidative stress plays an important role in the pathophysiology of diabetes mellitus. The aim of this study was to evaluate the formation of cholesterol oxides (ChOx) as biomarkers of oxidative stress in subjects with impaired glucose tolerance (IGT) and diabetes.Methods Blood plasma levels of cholesterol oxidation products were determined in the following groups: type I diabetes mellitus (DM1), type 2 diabetes (DM2), impaired glucose tolerance (IGT), children without diabetes (Cl) and adults without diabetes (C2). The serum levels of cholest-5-ene-3 alpha,7 alpha-diol (7 alpha-hydroxycholesterol, 7 alpha-OH), cholest-5-ene-3 beta,7 beta-diol (7 beta-hydroxycholesterol, 7 beta-OH), 3 beta-hydroxycholest-5-7-one (7-ketocholesterol, 7-K),5 alpha-cholestane-3 beta,5,6 beta-triol (cholestanetriol), 5,6 alpha-epoxy-5 alpha-cholestan-3 alpha-ol (cholesterol-5 alpha, 6 alpha-epoxide,), 5,6 beta-epoxy-5 beta-cholestan-3 beta-ol (cholesterol-5 beta,6 beta-epoxide) and cholest-5-eno-3 beta,25-diol (25-hydroxycholesterol, 25-OH) (trivial name and abbreviations indicated in parentheses) were quantified by gas chromatography using flame ionization detection.Results The levels of total ChOx were elevated in the DM1 and DM2 groups compared to age-matched subjects without diabetes (p < 0.05). The concentrations of 7 beta-hydroxycholesterol, cholesterol-alpha-epoxide and cholesterol-beta-epoxide were higher in the blood plasma of subjects in the DM2 group than in the blood plasma of subjects in the C2 and IGT groups (p < 0.05). Treatment of type 2 diabetic patients with oral hypoglycemic drugs associated with insulin resulted in lower concentrations of nitrotyrosine in the blood plasma without significant changes in the concentrations of glucose and glycated hemoglobin. Moreover combination with statins in, both treatments decreased the concentrations of ChOx.Conclusions ChOx are suitable biomarkers of oxidative stress and may be useful in clinical studies to follow drug effects on lipid oxidative modifications in diabetic patients. Copyright (c) 2006 John Wiley & Sons, Ltd.