effect using antioxidant vitamins (e.g. tocopherol and ascorbic acids [8,9]), minerals (e.g. zinc), flavanols [10,11] and soy [12]. Because it is also postulated that the generation of isoprostanoids is associated with inflam- mation, subsequent studies on the use of omega-3 poly- unsaturated fatty acids (PUFAs) emerged [13]. However, in the view of nutritionists and food scientists, it is not a single nutrient factor from the diet that acts as an anti- oxidant, but the whole food or the extract of the whole food, i.e. functional foods, that have a better effect in reducing oxidative stress. It is also known that the measurement of isoprostanoids requires robust but expensive mass spectrometry instru- mentation, such as gas chromatography-mass spectrome- try (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), for assessment in human plasma and urine samples [14,15]. Thus, many studies have relied on enzyme-linked immunosorbent assay Special Issue on “Analytical Methods for Oxidized Biomolecules and Antioxidants” The use of isoprostanoids as biomarkers of oxidative damage, and their role in human dietary intervention studies J.-M. Galano 1 , Y. Y. Lee 2 , T. Durand 1 & J. C.-Y. Lee 2 1 Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, ENSCM, Universités of Montpellier, France and 2 School of Biological Sciences, The University of Hong Kong, Hong Kong, China Abstract Isoprostanoids are a group of non-enzymatic oxidized lipids from polyunsaturated fatty acids. They are commonly used as biomarkers for oxidative damage, to assess in vivo lipid peroxidation in diseases related to the vascular system and neurodegeneration. Currently, there is a mismatch with the outcome in the use of these biomarkers in intervention studies, particularly when testing the effect of antioxidants such as vitamins C and E, or zinc, or a cocktail of these, with other food components. Much of this is because the biomarkers, the method of measurement, and the duration of supplementation are unsuitable. In this review, we will highlight the formation of isoprostanoids from their respective fatty acids, and their application as biomarkers for oxidative damage in vivo, considering human dietary intervention studies evaluating plasma and urine, using mass spectrometry techniques. Keywords: isoprostanes, dihomo-isoprostanes, neuroprostanes, phytoprostanes, antioxidants, mass spectrometry Abbreviations: 2,3-dinor-15-F 2t -IsoP, 2,3-dinor-15-F 2t -isoprostane; 2,3-dinor-5,6-dihydro-15-F 2t -IsoP, 2,3-dinor-5,6-dihydro-15-F 2t - isoprostane; 4(RS)-4-F 4t -NeuroP, 4(RS)-4-F 4t -neuroprostane; 5-F 2c -IsoP, 5-F 2c -isoprostane; 5-F 3t -IsoP, 5-F 3t -isoprostane; 8-F 3t -IsoP, 8-F 3t - isoprostane; 10-F 4t -NeuroP, 10-F 4t -neuroprostane; 15-F 2t -IsoP, 15-F 2t -isoprostane; 15-F 3t -IsoP, 15-F 3t -isoprostane; 17-F 2t -dihomo-IsoP, 17(RS)-17-F 2t -dihomo-isoprostane; ent-7-F 2t -dihomo-IsoP, 7(RS)-7-F 2t -dihomo-isoprostane; AA, arachidonic acid; AD, Alzheimer’s disease; AdA, adrenic acid; CoQ, coenzyme Q; COX, cyclooxygenase; CSF, cerebral spinal fluid; DHA, docosahexaenoic acid; dihomo-IsoPs, dihomo-isoprostanes; ELISA, enzyme-linked immunosorbent assay; EPA, eicosapentaenoic acid; F 2 -IsoPs, F 2 -isoprostanes; F 3 -IsoPs, F 3 - isoprostanes; F 4 -NeuroPs, F 4 -neuroprostanes; GC-MS, gas chromatography-mass spectrometry; GSH, glutathione; H 2 O 2 , hydrogen peroxide; IsoFs, isofurans; IsoPs, isoprostanes; LC-MS/MS, liquid chromatography-tandem mass spectrometry; MUFA, monounsaturated fatty acid; NeuroPs, neuroprostanes; NICI, negative chemical ionization; PG, prostaglandins; PUFA, polyunsaturated fatty acid; SOD, superoxide dismutase Introduction The discovery of isoprostanoids by Morrow et al . [1] dur- ing the 1990s has revolutionized the study of free radical reactions in lipid metabolism. That group, and others, have witnessed the importance of isoprostanoids as oxidative damage biomarkers in vivo and in many metabolic disor- ders such as cancer [2], type 2 diabetes [3], cardiovascular disease [4], and neurodegeneration [5,6]. Therefore, it is assumed that excess isoprostanoids in vivo is a disadvan- tage for general health and well-being. Nevertheless, this viewpoint is currently being modified by the identification of F 4 -NeuroPs in reducing the risk of atherosclerosis and cardiovascular disease [4,7]. Alternatively, little is known concerning the robust- ness in the measurement of these isoprostanoids in stud- ies that involve dietary intervention. Indeed, these interventions were mainly focused on the antioxidant Correspondence: Dr. Jetty Chung-Yung Lee, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China. Tel: + 852 2299 0318. Fax: + 852 2559 9114. E-mail: jettylee@hku.hk (Received date: 7 October 2014; Accepted date: 12 January 2015; Published online: ◾◾◾) Free Radical Research, 2015; Early Online: 1–16 © 2015 Informa UK, Ltd. ISSN 1071-5762 print/ISSN 1029-2470 online DOI: 10.3109/10715762.2015.1007969 REVIEW ARTICLE Free Radic Res Downloaded from informahealthcare.com by University of Hong Kong Libraries on 03/03/15 For personal use only.