A class of prostaglandin-like compounds, called isoprostanes, are formed by a free-radical catalyzed mechanism. In normal humans, levels of one isoprostane (8-iso-Prostaglandin F2a) range from 5-50 pg/mL plasma and 500-3000 pg/mg urinary creatinine, respectively. The in vivo concentration of F2-isoprostanes increases dramatically in animal models of oxidant stress, and available evidence strongly suggests that isoprostane analyses have significant potential for assessment of human oxidative stress and susceptibility to rheumatoid arthritis, atherosclerosis and cancer. Recent studies indicate that a large percentage of free F2 isoprostanes detected in urine is produced locally by the kidney, whereas F2 isoprostanes derived from systemic oxidant stress appear to be largely metabolized to other compounds before excretion. 2,3-dinor-5,6-dihydro-8- iso-prostaglandin F2alpha (DDIP), the major urinary metabolite of 8-iso- Prostaglandin F2alpha in human urine, may be an excellent marker for systemic oxidant stress. Development of a sensitive and specific immunoassay for DDIP should provide a simple non-invasive method for routine quantitative assessment of oxidant stress. Such as assay will aid in evaluating the biochemical consequences of antioxidant consumption, exercise, and environmental factors. In Phase I research, we ill synthesize and characterize DDIP, generate polyclonal antisera to DDIP, and develop an enzyme-linked immunoSorbent Assay (ELISA) for DDIP.
