Isoprostanes: markers and mediators of oxidative stress

Abstract

Some years ago it was discovered that prostaglandin F 2 ‐like compounds are formed in vivo by nonenzymatic free radical‐catalyzed peroxidation of arachidonic acid. Because these compounds are a series of isomers that contain the prostane ring of prostaglandins, they were termed F 2 ‐isoprostanes. Intermediates in the isoprostane pathway are prostaglandin H 2 ‐like compounds that become reduced to form F 2 ‐isoprostanes but also undergo rearrangement in vivo to form E 2 ‐, D 2 ‐, A 2 ‐, J 2 ‐isoprostanes, isothromboxanes, and highly reactive γ ‐ketoaldehydes, termed isoketals. Analogous compounds have also been shown to be formed from free radical mediated oxidation of docosoahexaenoic acid. Because docosahexaenoic acid is highly enriched in neurons, these compounds have been termed neuroprostanes and neuroketals. An important aspect of the discovery of isoprostanes is that measurement of F 2 ‐isoprostanes has emerged as one of the most reliable approaches to assess oxidative stress status in vivo, providing an important tool to explore the role of oxidative stress in the pathogenesis of human disease. Measurement of F 4 ‐neuroprostanes has also proved of value in exploring the role of oxidative stress in neurodegenerative diseases. Products of the isoprostane pathway have been found to exert potent biological actions and therefore may participate as physiological mediators of disease.—Montuschi, P., Barnes, P. J., Roberts, L J., II. Isoprostanes: markers and mediators of oxidative stress. FASEB J. 18, 1791‐1800 (2004 )