Isofurans: Novel products of lipid peroxidation that define the occurrence of oxidant injury in settings of elevated oxygen tension

We recently reported the discovery of isofurans, novel products of free radical-induced peroxidation of arachidonic acid that exhibit favored formation with increasing oxygen concentrations. In this review, the biochemistry of isofuran formation is compared with that of isoprostanes, with an emphasis on the mechanistic basis for the favored formation of isofurans at elevated oxygen tensions. In addition, the formation of isofurans in various disease states in vivo is also discussed. Parkinson's disease is presented as a disease model involving mitochondrial dysfunction, a situation in which quantification of isofurans can provide a uniquely sensitive indicator of oxidant injury. Measurement of isofurans has also provided unexpected insights into the earliest events in hyperoxic lung injury, an important clinical problem in which measurement of isofurans might prove to be uniquely valuable in the evaluation of approaches to limit this injury. These two settings are then used as models to suggest a variety of other pathological settings in which measurement of isofurans together with isoprostanes could provide a complete and robust picture of oxidative stress status in ongoing and future investigations.