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1
Division of Clinical Biochemistry and Human Metabolism and the Center for Human Nutrition, Department of Pathology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9073.
2
Clinical Nutrition Research Unit, Vanderbilt University Medical Center, C-2104 MCN, Nashville, TN 37232-2279.
aAddress correspondence to this author at: Division of Clinical Biochemistry and Human Metabolism, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9073. Fax 214-648-8037; e-mail jialal.i{at}pathology.swmed.edu.
Background: Oxidative stress is pivotal in atherogenesis. Although the most widely used indirect assay to quantify oxidative stress is LDL oxidative susceptibility, direct assays such as urinary F2-isoprostanes have shown great promise.
Methods: We evaluated the utility of both a direct measure of oxidative stress (urinary F2-isoprostanes) and an indirect measure of copper-catalyzed, LDL oxidation in a model of increased oxidative stress (diabetes). We also evaluated an enzyme immunoassay (EIA) method for urinary F2-isoprostanes with a gas chromatography–mass spectrometry method.
Results: Excellent intraassay and interassay CVs of <4% were obtained with our EIA method. A good correlation was obtained between the two methods (r = 0.80; n = 68) of F2-isoprostane measurement. An excellent correlation for F2-isoprostane concentrations was obtained between a timed collection vs 24-h urine (r = 0.96; n = 46). Baseline F2-isoprostane concentrations by EIA were significantly higher in both type 2 diabetics with and without macrovascular complications compared with controls (P <0.001). Supplementation with 
-tocopherol led to a significant reduction in F2-isoprostane concentrations in all diabetic patients compared with baseline values (2.51 ± 1.76 compared with 1.69 ± 1.32 ng/mg creatinine; P <0.001). There were no significant differences in LDL oxidation in both diabetic groups compared with controls. -Tocopherol supplementation led to significant increases in the lag phase of oxidation as measured by 3 indices in all groups.
Conclusions: The measurement of urinary F2-isoprostanes provides a direct measure of in vivo lipid peroxidation and oxidative stress and appears to be superior to an indirect measure, e.g., LDL oxidative susceptibility, in type 2 diabetes.
The following articles in journals at HighWire Press have cited this article:
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I. S. Young Oxidative Stress and Vascular Disease: Insights from Isoprostane Measurement Clin. Chem., January 1, 2005; 51(1): 14 - 15. [Full Text] [PDF]
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D. J O'Byrne, S. Devaraj, S. M Grundy, and I. Jialal Comparison of the antioxidant effects of Concord grape juice flavonoids {alpha}-tocopherol on markers of oxidative stress in healthy adults Am. J. Clinical Nutrition, December 1, 2002; 76(6): 1367 - 1374. [Abstract] [Full Text] [PDF]
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 S. Devaraj, A. V. C. Chan Jr., and I. Jialal {alpha}-Tocopherol Supplementation Decreases Plasminogen Activator Inhibitor-1 and P-Selectin Levels in Type 2 Diabetic Patients Diabetes Care, March 1, 2002; 25(3): 524 - 529. [Abstract] [Full Text] [PDF]
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