Novel Eicosapentaenoic Acid-derived F3-isoprostanes as Biomarkers of Lipid Peroxidation

Isoprostanes (iPs) are prostaglandin (PG) isomers generated by free radical-catalyzed peroxidation of polyunsaturated fatty acids (PUFAs). Urinary F2-iPs, PGF2α isomers derived from arachidonic acid (AA) are used as indices of lipid peroxidation in vivo. We now report the characterization of two maj...

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Bibliographic Details
Published in:The Journal of biological chemistry 2009-08, Vol.284 (35), p.23636-23643
Main Authors: Song, Wen-Liang, Paschos, Georgios, Fries, Susanne, Reilly, Muredach P., Yu, Ying, Rokach, Joshua, Chang, Chih-Tsung, Patel, Pranav, Lawson, John A., FitzGerald, Garret A.
Format: Article
Language:English
Subjects:
Animals
Biomarkers - chemistry
Biomarkers - metabolism
Biomarkers - urine
Eicosapentaenoic Acid - chemistry
Eicosapentaenoic Acid - metabolism
Female
Humans
Isomerism
Isoprostanes - chemistry
Isoprostanes - metabolism
Isoprostanes - urine
Lipid Peroxidation
Lipids and Lipoproteins: Metabolism, Regulation, and Signaling
Male
Mice
Mice, Inbred C57BL
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Summary:Isoprostanes (iPs) are prostaglandin (PG) isomers generated by free radical-catalyzed peroxidation of polyunsaturated fatty acids (PUFAs). Urinary F2-iPs, PGF2α isomers derived from arachidonic acid (AA) are used as indices of lipid peroxidation in vivo. We now report the characterization of two major F3-iPs, 5-epi-8,12-iso-iPF3α-VI and 8,12-iso-iPF3α-VI, derived from the ω-3 fatty acid, eicosapentaenoic acid (EPA). Although the potential therapeutic benefits of EPA receive much attention, a shift toward a diet rich in ω-3 PUFAs may also predispose to enhanced lipid peroxidation. Urinary 5-epi-8,12-iso-iPF3α-VI and 8,12-iso-iPF3α-VI are highly correlated and unaltered by cyclooxygenase inhibition in humans. Fish oil dose-dependently elevates urinary F3-iPs in mice and a shift in dietary ω-3/ω-6 PUFAs is reflected by an increasing slope [m] of the line relating urinary 8, 12-iso-iPF3α-VI and 8,12-iso-iPF2α-VI. Administration of bacterial lipopolysaccharide evokes a reversible increase in both urinary 8,12-iso-iPF3α-VI and 8,12-iso-iPF2α-VI in humans on an ad lib diet. However, while excretion of the iPs is highly correlated (R2 median = 0.8), [m] varies by an order of magnitude, reflecting marked inter-individual variability in the relative peroxidation of ω-3 versus ω-6 substrates. Clustered analysis of F2- and F3-iPs refines assessment of the oxidant stress response to an inflammatory stimulus in vivo by integrating variability in dietary intake of ω-3/ω-6 PUFAs.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M109.024075