Assessment of oxidant stress in allergic asthma by measurement of the major urinary metabolite of F2‐isoprostane, 15‐F2t‐IsoP (8‐iso‐PGF2α)

Abstract

Asthma is a chronic inflammatory disease of the airways which may involve an oxidant injury to the lung. Assessment of oxidant stress is difficult in vivo, but measurement of F₂-isoprostanes (F₂-IsoPs), free radical-catalysed products of arachidonic acid, appears to offer a reliable approach for quantitative measurement of oxidative stress status in vivo. We have recently developed a mass spectrometric assay for 2,3-dinor-5,6-dihydro-15-F_2t-IsoP (15-F_2t-IsoP-M), the major urinary metabolite of the F₂-IsoP, 15-F_2t-IsoP (8-iso-PGF_2a). Measurement of the urinary excretion of this metabolite offers a reliable index of oxidative stress status in vivo that has advantages over measuring unmetabolized F₂-IsoPs in urine and plasma. To assess the occurrence of oxidative stress in patients with atopic asthma following allergen exposure in vivo by measuring the urinary excretion of 15-F_2t-IsoP-M. Analysis of 15-F_2t-IsoP-M by GC-NICI-MS in nine mild atopic asthmatics following inhaled allergen provocation and four asthmatic subjects after inhaled challenge with methacholine. Urinary excretion of 15-F_2t-IsoP-M increased at 2 h after allergen challenge and remained significantly elevated in all urine collections during the subsequent 8-h period of the study compared to the baseline value (anova, and Student–Newman–Keuls multiple comparisons test). No increase in the urinary excretion of 15-F_2t-IsoP-M occurred after inhalation of methacholine. Allergen challenge causes an oxidant injury in human atopic asthmatics. 15-F_2t-IsoP-M is a valuable marker of oxidant stress in vivo.