Quantitative analysis of f(2) isoprostanes

The discoveries by Jack Roberts and Jason Morrow of the nonenzymatic oxidation of cell membrane phospholipids to form isoprostanes has revolutionized the field of eicosanoids (1). Prior to their discoveries, it was dogma that the important biologically active eicosanoids were formed by enzymes acting on arachidonic acid that had been cleaved from phospholipids by the action of phospholipases. Their research has clearly shown that important biologically active fatty acid metabolites are formed in a variety of inflammatory conditions from the action of oxygen radicals on arachidonic acid, while it is still present in complex phospholipids. These oxidized compounds may alter cell structure and signaling, and when released by the action of phospholipases, are immediately available to bind to receptors to modulate cell activity. The free radical attack on arachidonate yields an endoperoxide which can then be transformed nonenzymatically to F, D, E ring prostaglandins. Thus, each enzymatically formed eicosanoid appears to have its own class of isoprostanes, including isothromboxanes (2,3). Likewise, the isoleukotrienes have been described. In addition, compounds such as the hydroxyeicosatetraenoic acids (HETEs) can also be formed in this fashion (4,5). The biologic activity of these compounds is only now being examined.