Loading…
Identification of non-cyclooxygenase-derived prostanoid (F2-isoprostane) metabolites in human urine and plasma
Free radicals are thought to play an important role in many types of tissue injury. Recently, we reported that a series of prostaglandin F2-like compounds (F2-isoprostanes) capable of exerting potent biological activity are produced in vivo by free radical-induced lipid peroxidation. Their formation...
Saved in:
Published in: | The Journal of biological chemistry 1993-02, Vol.268 (6), p.4161-4169 |
---|---|
Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | Free radicals are thought to play an important role in many types of tissue injury. Recently, we reported that a series of
prostaglandin F2-like compounds (F2-isoprostanes) capable of exerting potent biological activity are produced in vivo by free
radical-induced lipid peroxidation. Their formation is independent of the cyclooxygenase enzyme and has been shown to increase
profoundly in animal models of free radical injury and lipid peroxidation. We now report the identification of F-ring isoprostane
metabolites in human urine and plasma utilizing a gas chromatographic/mass spectrometric assay for the major urinary metabolite
of prostaglandin D2 (9 alpha,11 beta-dihydroxy-15-oxo-2,3, 18,19-tetranorprost-5-ene-1,20-dioic acid). Evidence confirming
these metabolites as tetranor, dicarboxylic acid compounds containing one double bond, cis-cyclopentane ring hydroxyls, and
one keto group similar in structure to the major urinary metabolite of prostaglandin D2 was obtained by analysis of human
urine by electron ionization mass spectrometry. Levels of these metabolites in normal human urine were determined and found
to be unaffected by cyclooxygenase inhibitors. Evidence that these metabolites arise from F2-isoprostanes was obtained by
demonstrating that (a) marked increases in plasma levels and urinary excretion of these metabolites, which were unaffected
by coadministration of indomethacin, occurred in rats administered CCl4 to induce F2-isoprostane formation and (b) marked
increases in levels of these metabolites in plasma and urine resulted from the intravenous infusion of F2-isoprostanes into
a rat. Quantification of these isoprostane metabolites in urine and plasma may provide a reliable index of endogenous isoprostane
production which could prove to be an important advance in our ability to assess oxidant stress in vivo in humans. |
---|---|
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/s0021-9258(18)53593-6 |