title: Specific analysis in plasma and urine of 2,3-dinor-5, 6-dihydro-isoprostane F(2alpha)-III, a metabolite of isoprostane F(2alpha)-III and an oxidation product of gamma-linolenic acid.
abstract: F(2)-isoprostanes (iPs) are free radical-catalyzed isomers of prostaglandin F(2alpha). Circulating and urinary iPs have been used as indices of lipid peroxidation in vivo. Utilizing an (18)O-labeled homologous internal standard, we developed a gas chromatography/mass spectrometry assay for the 2,3-dinor-5,6-dihydro (dinor-dihydro) metabolite of iPF(2alpha)-III. Although urinary excretion of iPF(2alpha)-III reflects systemic lipid peroxidation, the metabolite is more abundant (median of 877 (range of 351-1831) versus 174 (range of 56-321) pg/mg of creatinine; p < 0.01) than the parent iP in urine and can be measured in plasma. Metabolite analysis may be preferable in plasma due to the abundance of arachidonic acid as a source of ex vivo lipid peroxidation. Also, iPF(2alpha)-III may be formed in blood samples in a cyclooxygenase-dependent manner by platelets ex vivo. By contrast, the metabolite is not formed by aggregated platelets (0.71 +/- 0.08 versus 0.65 +/- 0.09 pg/ml). Although the metabolite/parent ratio is altered in cirrhosis, urinary dinor-dihydro-iPF(2alpha)-III is elevated and increases further during reperfusion following orthoptic liver transplantation. In addition to its formation as an iPF(2) metabolite, analysis of gamma-linolenic acid autooxidation products and the compound present in freeze-thawed plasma suggests that gamma-linolenic acid may also be an important source of dinor-dihydro-iPF(2alpha)-III.
authors.affiliation: Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: A
authors.initials: A
authors.lastname: Burke
authors.forename: J A
authors.initials: JA
authors.lastname: Lawson
authors.forename: E A
authors.initials: EA
authors.lastname: Meagher
authors.forename: J
authors.initials: J
authors.lastname: Rokach
authors.forename: G A
authors.initials: GA
authors.lastname: FitzGerald
mesh_terms: D000328:Adult; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000652:urine; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D012680:Sensitivity and Specificity; D017965:gamma-Linolenic Acid / Q000378:metabolism*
chemical_list: C404185:2,3-dinor-5,6-dihydroisoprostane F2alpha-III; D017965:gamma-Linolenic Acid; D015237:Dinoprost