Analysis of 19 urinary biomarkers of oxidative stress, nitrative stress, metabolic disorders, and inflammation using liquid chromatography-tandem mass spectrometry

摘要

Environmental chemical exposures have been associated with cancer, diabetes, hormonal and immunological disorders, and cardiovascular diseases. Some direct effects of chemical exposure that are precursors to adverse health outcomes, including oxidative stress, nitrative stress, hormonal imbalance, neutrophilia, and eosinophilia, can be assessed through the analysis of biomarkers in urine. In this study, we describe a novel methodology for the determination of 19 biomarkers of health effects: malondialdehyde (MDA), 8-isoprostaglandin-F-2 alpha (8-PGF(2 alpha)), 11-beta-prostaglandin-F-2 alpha (11-PGF(2 alpha)), 15-prostaglandin-F-2 alpha (15-PGF(2 alpha)), 8-iso-15-prostaglandin-F-2 alpha (8,15-PGF(2 alpha)), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-HdG), 8-hydroxyguanine (8-HG), dityrosine (diY), allantoin (Alla), and two metabolic products of 4-hydroxynonenal (HNE), namely 4-hydroxy-2-nonenal glutathione (HNE-GSH) and 4-hydroxy-2-nonenal mercapturic acid (HNE-MA) (in total, 12 oxidative stress biomarkers, OSBs); 8-nitroguanosine (8-NdG), 8-nitroguanine (8-NG), and 3-nitrotyrosine (NY) (3 nitrative stress biomarkers, NSBs); chlorotyrosine (CY) and bromotyrosine (BY) (2 inflammatory biomarkers); and the advanced glycation end-products (AGEs) N-epsilon-carboxymethyllysine (CML) and N-epsilon-carboxyethyllysine (CEL) (2 metabolic disorder biomarkers). Since these biomarkers are trigged by a variety of environmental insults and produced by different biomolecular pathways, their selective and sensitive determination in urine would help broadly elucidate the pathogenesis of diseases mediated by environmental factors.