title: Dihomo-isoprostanes-nonenzymatic metabolites of AdA-are higher in epileptic patients compared to healthy individuals by a new ultrahigh pressure liquid chromatography-triple quadrupole-tandem mass spectrometry method.
abstract: Oxidative stress is a biochemical state in which reactive oxygen species are generated and it has been associated with pathological states including epilepsy. Therein, neuroprostanes (NeuroPs) and dihomo-isoprostanes (Dihomo-IsoPs)-a series of compounds formed nonenzymatically through free radical-induced DHA, n-6 DPA, and AdA peroxidation-are implicated in the pathophysiological status of various human neurological diseases. A new, robust, and selective analytical method for the determination of 10 NeuroPs/Dihomo-IsoPs in human urine, using solid-phase extraction and UHPLC-QqQ-MS/MS in the multiple reaction monitoring mode (using a negative electrospray ionization interface), was developed. Nine NeuroPs/Dihomo-IsoPs were identified in 15 epileptic patients, matched with healthy volunteers. Among them, 17-F2t-Dihomo-IsoP, Ent-7(R)-7-F2t-Dihomo-IsoP, and Ent-7-epi-7-F2t-Dihomo-IsoP, derived from adrenic acid (AdA), were significantly higher in epileptic patients than in healthy volunteers. The validated method provided a high-throughput assay with a limit of detection and limit of quantification for each analyte of 0.10-5.90ngmL(-1) and 0.15-11.81ngmL(-1), respectively. The intra- and interday variations were lower than 14%. Dihomo-IsoPs have been considered as potential markers of epilepsy for the first time and their measurement may increase the understanding of the role of oxidative stress in neurological diseases, in intra vitam studies. The present study highlights a potential role of Dihomo-IsoPs as biomarkers in persons with epilepsy, though its mechanisms and possible implications should be the subject of further investigations.
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS (CSIC), P.O. Box 164, 30100 Campus University Espinardo, Murcia, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Medina
authors.affiliation: Lab of Clinical Analysis, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors.forename: Irene De
authors.initials: ID
authors.lastname: Miguel-Elízaga
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247-CNRS-University Montpellier I and II-ENSCM, Faculty of Pharmacy, Montpellier, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Oger
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247-CNRS-University Montpellier I and II-ENSCM, Faculty of Pharmacy, Montpellier, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Galano
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247-CNRS-University Montpellier I and II-ENSCM, Faculty of Pharmacy, Montpellier, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Durand
authors.affiliation: Lab of Clinical Analysis, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Martínez-Villanueva
authors.affiliation: Lab of Clinical Analysis, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors.forename: María Luisa Gil-Del
authors.initials: ML
authors.lastname: Castillo
authors.affiliation: Epilepsy Unit, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Villegas-Martínez
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS (CSIC), P.O. Box 164, 30100 Campus University Espinardo, Murcia, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Ferreres
authors.affiliation: Lab of Clinical Analysis, University Hospital Virgen de la Arrixaca, Murcia, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Martínez-Hernández
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS (CSIC), P.O. Box 164, 30100 Campus University Espinardo, Murcia, Spain. Electronic address: angelgil@cebas.csic.es.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Gil-Izquierdo
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000652:urine*; D002138:Calibration; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004827:Epilepsy / Q000652:urine*; D005260:Female; D006801:Humans; D006868:Hydrolysis; D028421:Isoprostanes / Q000652:urine*; D008297:Male; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D015415:Biomarkers; D028421:Isoprostanes
keywords: Dihomo-isoprostanes; Epilepsy; Free radicals; Methods; Neuroprostanes; Oxidative stress; UHPLC–QqQ–MS/MS; Urine