title: Novel eicosapentaenoic acid-derived F3-isoprostanes as biomarkers of lipid peroxidation.
abstract: Isoprostanes (iPs) are prostaglandin (PG) isomers generated by free radical-catalyzed peroxidation of polyunsaturated fatty acids (PUFAs). Urinary F(2)-iPs, PGF(2alpha) isomers derived from arachidonic acid (AA) are used as indices of lipid peroxidation in vivo. We now report the characterization of two major F(3)-iPs, 5-epi-8,12-iso-iPF(3alpha)-VI and 8,12-iso-iPF(3alpha)-VI, derived from the omega-3 fatty acid, eicosapentaenoic acid (EPA). Although the potential therapeutic benefits of EPA receive much attention, a shift toward a diet rich in omega-3 PUFAs may also predispose to enhanced lipid peroxidation. Urinary 5-epi-8,12-iso-iPF(3alpha)-VI and 8,12-iso-iPF(3alpha)-VI are highly correlated and unaltered by cyclooxygenase inhibition in humans. Fish oil dose-dependently elevates urinary F(3)-iPs in mice and a shift in dietary omega-3/omega-6 PUFAs is reflected by an increasing slope [m] of the line relating urinary 8, 12-iso-iPF(3alpha)-VI and 8,12-iso-iPF(2alpha)-VI. Administration of bacterial lipopolysaccharide evokes a reversible increase in both urinary 8,12-iso-iPF(3alpha)-VI and 8,12-iso-iPF(2alpha)-VI in humans on an ad lib diet. However, while excretion of the iPs is highly correlated (R(2) median = 0.8), [m] varies by an order of magnitude, reflecting marked inter-individual variability in the relative peroxidation of omega-3 versus omega-6 substrates. Clustered analysis of F(2)- and F(3)-iPs refines assessment of the oxidant stress response to an inflammatory stimulus in vivo by integrating variability in dietary intake of omega-3/omega-6 PUFAs.
authors.affiliation: Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Song
authors.forename: Georgios
authors.initials: G
authors.lastname: Paschos
authors.forename: Susanne
authors.initials: S
authors.lastname: Fries
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.forename: Joshua
authors.initials: J
authors.lastname: Rokach
authors.forename: Chih-Tsung
authors.initials: CT
authors.lastname: Chang
authors.forename: Pranav
authors.initials: P
authors.lastname: Patel
authors.forename: John A
authors.initials: JA
authors.lastname: Lawson
authors.forename: Garret A
authors.initials: GA
authors.lastname: Fitzgerald
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D015118:Eicosapentaenoic Acid / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D007536:Isomerism; D028421:Isoprostanes / Q000737:chemistry* / Q000378:metabolism* / Q000652:urine; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D015415:Biomarkers; D028421:Isoprostanes; D015118:Eicosapentaenoic Acid