Identification and measurement of endogenous β-oxidation metabolites of 8-epi-prostaglandin F2α

Chiara Chiabrando, Anna Valagussa, Claudia Rivaltat, Thierry Durand, Alexandre Guy, Ettore Zuccato, Pia Villa, Jean Claude Rossi, Roberto Fanelli

Research output: Contribution to journalArticle

Abstract

F2-isoprostanes are prostaglandin-like compounds derived from nonenzymatic free radical-catalyzed peroxidation of arachidonic acid. 8-epi- Prostaglandin (PG) F(2α), a major component of the F2-isoprostane family, can be conveniently measured in urine to assess noninvasively lipid peroxidation in vivo. Measurement of major metabolites of endogenous 8-epi- PGF(2α), in addition to the parent compound, may be useful to better define its formation in vivo. 2,3-Dinor-5,6-dihydro-8-epi-PGF(2α) is the only identified metabolite of 8-epi-PGF(2α) in man, but its endogenous levels are unknown. In addition to this metabolite, we have identified another major endogenous metabolite, 2,3-dino-8-epi-PGF(2α), in human and rat urine. The identity of these compounds, present at the pg/ml level in urine, was proven by a number of complementary approaches, based on: (a) immunoaffinity chromatography for selective extraction; (b) gas chromatography-mass spectrometry for structural analysis; (c) in vitro metabolism in isolated rat hepatocytes; and (d) chemical synthesis of the enantiomer of 2,3-dinor-5,6- dihydro-8-epi-PGF(2α) as a reference standard. In humans, the urinary excretion rate of both dinor metabolites is comparable with that of 8-epi- PGF(2α). Both metabolites increase in parallel with the parent compound in cigarette smokers, and they are not reduced during cyclooxygenase inhibition. Another β-oxidation product, 2,3,4,5-tetranor-8-epi-PGF(2α), was identified as a major product of rat hepatocyte metabolism. In conclusion, at least two major β-oxidation products of 8-epi-PGF(2α) are present in urine, which may be considered as additional analytical targets to evaluate 8-epi-PGF(2α) formation and degradation in vivo.

Original languageEnglish
Pages (from-to)1313-1319
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number3
DOIs
Publication statusPublished - Jan 15 1999

ASJC Scopus subject areas

  • Biochemistry

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    Chiabrando, C., Valagussa, A., Rivaltat, C., Durand, T., Guy, A., Zuccato, E., Villa, P., Rossi, J. C., & Fanelli, R. (1999). Identification and measurement of endogenous β-oxidation metabolites of 8-epi-prostaglandin F2α. Journal of Biological Chemistry, 274(3), 1313-1319. https://doi.org/10.1074/jbc.274.3.1313