Measurement of F-2-isoprostanes as an index of oxidative stress in vivo

In 1990 we discovered the formation of prostaglandin F-2-like compounds, F- 2-isoprostanes (F-2-IsoPs), in vivo by nonenzymatic free radical-induced pe roxidation of arachidonic acid. F-2-IsoPs are initially formed esterified t o phospholipids and then released in free form. There are several favorable attributes that make measurement of F-2-IsoPs attractive as a reliable ind icator of oxidative stress in vivo: (i) F-2-IsoPs are specific products of Lipid peroxidation; (ii) they are stable compounds; (iii) levels are presen t in detectable quantities in all normal biological fluids and tissues, all owing the definition of a normal range; (iv) their formation increases dram atically 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 F-2-IsoPs in plasma can be utilized to assess total endogenous production of F-2-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 F-2-IsoPs, which should prov ide a valuable noninvasive integrated approach to assess total endogenous p roduction of F-2-IsoPs in large clinical studies. (C) 2000 Elsevier Science Inc.