F(2)-isoprostane and prostaglandin F(2 alpha)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.