A novel class of prostaglandin F2-like compounds formed in vitro or in vivo by a free-radical catalyzed noncyclooxygenase mechanism have recently been discovered. For normal humans, levels of these compounds (called F2-isoprostanes) range from 5-50 pg/mL plasma and 500-3000 pg/mg urinary creatinine, respectively. the in vivo concentration of F2- isoprostanes have been shown to increase dramatically in animal models of free-radical induced lipid peroxidation. Although the potential role(s) of isoprostanes in the pathophysiology of human diseases remain to be determined, preliminary evidence strongly suggests that measurement of isoprostane concentrations may have significant diagnostic potential for the assessment of oxidative stress and in specific disorders such as hepatorenal syndrome, rheumatoid arthritis, and carcinogenesis. Isoprostanes have thus far been detected by mass spectrometry. However, this is an expensive method that is not well suited for routine clinical determinations. In contrast, immunoassay is an established clinical procedure that is well suited for the detection of small amounts of specific fatty acid derivatives. The ultimate goal of the present proposal is the development of sensitive and specific immunoassays for isoprostanes that will facilitate (a) investigations of the physiologic and pathophysiologic roles of these compounds, and (b) clinical assessment of oxidative status.
