A novel class of prostaglandin-like compounds, called isoprostanes, formed in vitro or in vivo by a noncyclooxygenase-dependent free-radical catalyzed mechanism has recently been discovered. In normal humans, levels of one isoprostane (8-epi-Prostaglandin F2-alpha) 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 lipid peroxidation. Whereas the potential role of isoprostanes in the pathophysiology of human diseases remain to be determined, preliminary evidence strongly suggests that measurement of isoprostane concentrations has significant diagnostic potential for assessment of oxidative stress and disorders such as hepatorenal syndrome, rheumatoid arthritis, atherosclerosis and carcinogenesis. Isoprostanes have thus far been measured by mass spectrometry. However, this is an expensive method that is not well suited for routine clinical determinations. In contrast, immunoassays are established clinical procedures and are well suited for the detection of small amounts of specific fatty acid derivatives such as isoprostanes. The ultimate goal of this proposal is the development of sensitive and specific immunoassays for isoprostanes that will facilitate (a) investigations of the physiological and pathophysiological roles of these compounds, and (b) clinical assessment of oxidative status.
