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 peroxidation of arachidonic acid. F(2)-IsoPs are initially formed esterified to phospholipids and then released in free form. There are several favorable attributes that make measurement of F(2)-IsoPs attractive as a reliable indicator of oxidative stress in vivo: (i) F(2)-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 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 provide a valuable noninvasive integrated approach to assess total endogenous production of F(2)-IsoPs in large clinical studies.
Roberts
L J
LJ
Department of Pharmacology, Vanderbilt University, Nashville, TN, USA. jack.roberts@mcmail.vanderbilt.edu
Morrow
J D
JD
D000818:Animals; D015415:Biomarkers; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood / Q000652:urine; D006801:Humans; D015227:Lipid Peroxidation; D018384:Oxidative Stress
D015415:Biomarkers; D015237:Dinoprost