F2-isoprostane and prostaglandin F2α metabolite excretion rate and day to day variation in healthy humans

Isoprostanes are mainly formed in vivo by a non-enzymatic free radical catalysed oxidation of arachidonic acid. Studies have indicated that a major isoprostane, 8-iso-PGF(2 alpha) in plasma and urine is a reliable biomarker of oxidative stress. Prostaglandins are formed by enzymatic oxidation of arachidonic acid catalysed by cyclooxygenase (COX). 15-Keto-dihydro-PGF(2 alpha), a major metabolite of prostaglandin F-2 alpha, in plasma, and also found in urine, is considered to be a useful biomarker of inflammation. To investigate the excretion pattern and day to day variation of 8-iso-PGF(2 alpha), and 15-keto-dihydro-PGF(2 alpha) in healthy individuals, morning urine samples were collected from 13 volunteers on 10 successive days. The samples were analysed for free 8-iso-PGF(2 alpha) and 15-keto-dihydro-PGF(2 alpha) by radioimmunoassay. The mean excretion rate of 8-iso-PGF(2 alpha) was 0.27 +/-0.11 nmol/mmol creatinine (mean +/- SD, n=13) and the coefficient of variation was 42% during the 10 days. The mean excretion rate of 15-keto-dihydro-PGF(2 alpha) was 0.46 +/-0.19 nmol/mmol creatinine, giving a coefficient of variation of 41%. The mean values of 8-iso-PGF(2 alpha) were significantly correlated with the mean values of 15-keto-dihydro-PGF(2 alpha) (r=0.68, P=0.01). In conclusion, day to day biological variation in urinary excretion rate of 8-iso-PGF(2 alpha) and 15-keto-dihydro-PGF(2 alpha) should be taken into account in evaluating a clinical study unless a large increase or decrease of these parameters has been obtained. (C) 2001 Harcourt Publishers Ltd.