Recent advances in the biochemistry and clinical relevance of the isoprostane pathway

Isoprostanes (IsoPs), lipid peroxidation products formed via the free radical-mediated oxidation of arachidonic acid, have become the "gold standard" biomarker of oxidative stress in vivo over the past 15 yr. Significant advances have been made in understanding this important pathway of lipid peroxidation. Recent studies from our laboratory are discussed that have provided insights into the mechanism of formation and regioisomeric distribution of these compounds and that have identified novel products of the IsoP pathway such as cyclized dioxolane IsoPs, IsoP-derived racemic prostaglandins, and reactive cyclopentenone IsoP, the latter of which possess potent biological actions. Furthermore, new independent studies have demonstrated that IsoPs are the most reliable available marker of lipid peroxidation in vivo, and recent work examining IsoP formation has provided valuable information about the pathogenesis of numerous human diseases. Thus, the complexity of the IsoP pathway has expanded, providing novel insights into mechanisms of lipid peroxidation in vivo and allowing investigators to explore the role of oxidative stress in human disease.