Measurement of F2-isoprostanes as an index of oxidative stress in vivo

In 1990 we discovered the formation of prostaglandin F2-like compounds, F2-isoprostanes (F2-IsoPs), in vivo by nonenzymatic free radical–induced peroxidation of arachidonic acid. F2-IsoPs are initially formed esterified to phospholipids and then released in free form. There are several favorable attributes that make measurement of F2-IsoPs attractive as a reliable indicator of oxidative stress in vivo: (i) F2-IsoPs are specific products of lipid peroxidation; (ii) they are stable compounds; (iii) levels are present in detectable quantities in all normal biological fluids and tissues, allowing the definition of a normal range; (iv) their formation increases dramatically in vivo in a number of animal models of oxidant injury; (v) their formation is modulated by antioxidant status; and (vi) their levels are not effected by lipid content of the diet. Measurement of F2-IsoPs in plasma can be utilized to assess total endogenous production of F2-IsoPs whereas measurement of levels esterified in phospholipids can be used to determine the extent of lipid peroxidation in target sites of interest. Recently, we developed an assay for a urinary metabolite of F2-IsoPs, which should provide a valuable noninvasive integrated approach to assess total endogenous production of F2-IsoPs in large clinical studies.