Isoprostanes. Novel markers of endogenous lipid peroxidation and potential mediators of oxidant injury.

It was recently discovered that a series of structurally unique prostaglandin F2-like compounds (F2-isoprostanes) capable of exerting potent biological activity are produced in vivo in humans by a noncyclooxygenase mechanism involving free radical catalyzed peroxidation of arachidonic acid. Considerable evidence has been obtained suggesting that quantification of F2-isoprostanes represents an important advance in our ability to assess oxidant status in vivo in humans. This has allowed us to implicate oxidant stress in the pathogenesis of human disease-for example, the hepatorenal syndrome. In addition to the F2-isoprostanes, we recently discovered that E-ring and D-ring isoprostanes are also produced in abundance in vivo by rearrangement of the isoprostane endoperoxide intermediates. We have also been able to demonstrate that one of the E2-isoprostanes, 8-epi-PGE2, is a potent renal vasoconstrictor in the rat. Insights into factors that may influence the formation of E2/D2-isoprostanes relative to F2-isoprostanes should be important in advancing our understanding of the biological consequences of the formation of isoprostanes in vivo.