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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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  H.-Z. Pan, H. Zhang, D. Chang, H. Li, and H. Sui The change of oxidative stress products in diabetes mellitus and diabetic retinopathy Br. J. Ophthalmol., April 1, 2008; 92(4): 548 - 551. [Abstract] [Full Text] [PDF]
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 S. Devaraj, R. Tang, B. Adams-Huet, A. Harris, T. Seenivasan, J. A de Lemos, and I. Jialal Effect of high-dose {alpha}-tocopherol supplementation on biomarkers of oxidative stress and inflammation and carotid atherosclerosis in patients with coronary artery disease Am. J. Clinical Nutrition, November 1, 2007; 86(5): 1392 - 1398. [Abstract] [Full Text] [PDF]
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 D. Sircar and P. V. Subbaiah Isoprostane Measurement in Plasma and Urine by Liquid Chromatography-Mass Spectrometry with One-Step Sample Preparation Clin. Chem., February 1, 2007; 53(2): 251 - 258. [Abstract] [Full Text] [PDF]
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 A. Kontush and M. J. Chapman Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis Pharmacol. Rev., September 1, 2006; 58(3): 342 - 374. [Abstract] [Full Text] [PDF]
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 M. Brownlee and I. B. Hirsch Glycemic Variability: A Hemoglobin A1c-Independent Risk Factor for Diabetic Complications JAMA, April 12, 2006; 295(14): 1707 - 1708. [Full Text] [PDF]
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B. Wang, H. Zhu, H. Sun, J. Pan, Z. Yuan, and R. Yu Plasma 8-Isoprostane Concentrations in Patients with Age-Related Cataracts Clin. Chem., August 1, 2005; 51(8): 1541 - 1544. [Full Text] [PDF]
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 R. H Boger, E. Schwedhelm, R. Maas, S. Quispe-Bravo, and C. Skamira ADMA and oxidative stress may relate to the progression of renal disease: rationale and design of the VIVALDI study Vascular Medicine, May 1, 2005; 10(2_suppl): S97 - S102. [Abstract] [PDF]
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S. Vega-Lopez, K.-J. Yeum, J. L Lecker, L. M Ausman, E. J Johnson, S. Devaraj, I. Jialal, and A. H Lichtenstein Plasma antioxidant capacity in response to diets high in soy or animal protein with or without isoflavones Am. J. Clinical Nutrition, January 1, 2005; 81(1): 43 - 49. [Abstract] [Full Text] [PDF]
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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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 C. Vassalle, M. G. Andreassi, E. Schwedhelm, R. Maas, R. H. Boger, J. Brummer, J. Berger, A. Bartling, H. Lenzen, D. Tsikas, et al. 8-Iso-Prostaglandin F2{alpha} as a Risk Marker in Patients With Coronary Heart Disease * Response Circulation, August 3, 2004; 110(5): e49 - e50. [Full Text] [PDF]
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 A. M. Vincent, J. W. Russell, P. Low, and E. L. Feldman Oxidative Stress in the Pathogenesis of Diabetic Neuropathy Endocr. Rev., August 1, 2004; 25(4): 612 - 628. [Abstract] [Full Text] [PDF]
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 J. A. Beckman, A. B. Goldfine, M. B. Gordon, L. A. Garrett, J. F. Keaney Jr., and M. A. Creager Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2392 - H2398. [Abstract] [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. Mathur, S. Devaraj, S. M. Grundy, and I. Jialal Cocoa Products Decrease Low Density Lipoprotein Oxidative Susceptibility but Do Not Affect Biomarkers of Inflammation in Humans J. Nutr., December 1, 2002; 132(12): 3663 - 3667. [Abstract] [Full Text] [PDF]
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C. Hermenegildo, M. C. Garcia-Martinez, J. J. Tarin, and A. Cano Estradiol reduces F2alpha -isoprostane production in cultured human endothelial cells Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2644 - H2649. [Abstract] [Full Text] [PDF]
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M. J. Sheetz and G. L. King Molecular Understanding of Hyperglycemia's Adverse Effects for Diabetic Complications JAMA, November 27, 2002; 288(20): 2579 - 2588. [Abstract] [Full Text] [PDF]
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 S. K. Venugopal, S. Devaraj, T. Yang, and I. Jialal {alpha}-Tocopherol Decreases Superoxide Anion Release in Human Monocytes Under Hyperglycemic Conditions Via Inhibition of Protein Kinase C-{alpha} Diabetes, October 1, 2002; 51(10): 3049 - 3054. [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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