Isoprostanes: Generation, Pharmacology, and Roles in Free-radical-mediated Effects in the Lung

Isoprostanes are produced during peroxidation of membrane lipids by free radicals and reactive oxygen species, and are currently used as markers of many disease states and experimental conditions in which oxidative stress is a prominent feature. A small number of reports have described the ability of some isoprostanes to evoke important biological effects in smooth muscle and other cell types. However, most of these studies were done using rat tissues, and only two specific isoprostanes - 8-iso-PGE(2)and 8-iso-PGF(2alpha)- were tested. In this review, we describe the generation of isoprostanes during oxidative stress, and their effects on smooth muscle, including our novel findings of their effects on human airway, pulmonary artery and pulmonary vein smooth muscles. Collectively, the data suggest that isoprostanes may not only be markers, but may in fact mediate the effects of free radicals and reactive oxygen species.