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

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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‐F2t‐IsoP (15‐F2t‐IsoP‐M), the major urinary metabolite of the F2‐IsoP, 15‐F2t‐IsoP (8‐iso‐PGF2a). 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‐F2t‐IsoP‐M.Analysis of 15‐F2t‐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‐F2t‐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‐F2t‐IsoP‐M occurred after inhalation of methacholine.Allergen challenge causes an oxidant injury in human atopic asthmatics. 15‐F2t‐IsoP‐M is a valuable marker of oxidant stress in vivo.