Quantification of noncyclooxygenase derived prostanoids as a marker of oxidative stress.
Recently, we discovered there is a unique class of prostaglandin F2-like compounds that are formed in vitro from arachidonoyl-containing lipids in plasma by a free radical-catalyzed mechanism. More recent studies have elucidated that these prostanoids are also produced in vivo in humans by a similar noncyclooxygenase mechanism. Levels of these PGF2 compounds detected by a mass spectrometric assay in normal human plasma and urine range from approximately 5-50 pg/mL and 500-3000 pg/mg creatinine, respectively. Circulating levels of the compounds were shown to increase by as much as 200-fold in animal models of free radical-induced lipid peroxidation. These results suggest that quantification of these prostanoids may provide a new approach to assess oxidative stress in vivo in humans. Potential advantages of this approach are that the mass spectrometric assay has a high degree of sensitivity, accuracy, and specificity and the assay can be used to quantitate these compounds in a variety of biological fluids. In addition, quantification of these compounds is of interest because these compounds possess biological activity. Disadvantages of the assay are the potential of ex vivo formation of these compounds in biological fluids containing lipids and, further, these compounds must be differentiated from PGF2 compounds that are formed via the cyclooxygenase enzyme. In addition, because the levels of these compounds in normal human plasma and urine are relatively high, assaying these compounds in circulating plasma and urine may be somewhat insensitive for the detection of increased production at isolated sites of oxidant injury within the body, in which case sampling near localized sites of their formation may be required.(ABSTRACT TRUNCATED AT 250 WORDS)
Morrow
J D
JD
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232-6602.
Roberts
L J
LJ
D015415:Biomarkers; D015237:Dinoprost / Q000097:blood / Q000652:urine; D005609:Free Radicals; D006801:Humans; D015227:Lipid Peroxidation; D010100:Oxygen / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood / Q000652:urine; D011453:Prostaglandins / Q000032:analysis* / Q000097:blood / Q000652:urine; D013312:Stress, Physiological
D015415:Biomarkers; D005609:Free Radicals; D011453:Prostaglandins; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases; D010100:Oxygen