Identification of metabolites from type III F2-isoprostane diastereoisomers by mass spectrometry

Chiara Chiabrando, Claudia Rivalta, Renzo Bagnati, Anna Valagussa, Thierry Durand, Alexandre Guy, Pia Villa, Jean Claude Rossi, Roberto Fanelli

Research output: Contribution to journalArticlepeer-review

Abstract

F2-isoprostanes (F2-iPs) are prostaglandin (PG)-like products of non-enzymatic free radical-catalyzed peroxidation of arachidonic acid that are now widely used as indices of lipid peroxidation in vivo. Knowledge of the metabolic fate of F2-iPs in vivo is still scant, despite its importance for defining their overall formation and biological effects in vivo. Type III F2-iPs, which are diastereoisomers of cyclooxygenase-derived PGF, may be metabolized through the pathways of PG metabolism. We therefore studied the in vitro metabolism of eight synthetic Type III F2-iP diastereoisomers in comparison with PGF. We used gas chromatography-mass spectrometry and high performance liquid chromatography-electrospray-tandem mass spectrometry for structural identification of metabolites formed after incubation of the various compounds with isolated rat hepatocytes. PGF was metabolized to several known products, resulting from a combination of β-oxidation, reduction of Δ5 and/or Δ13 double bonds, and 15-OH oxidation, plus other novel products deriving from conjugation with taurine of PGF and its metabolites. Of the eight F2-iP diastereoisomers, some were processed similarly to PGF, whereas others showed peculiar metabolic profiles according to specific stereochemical configurations. These data represent the first evidence of biodegradation of selected Type III F2-iP isomers other than 8-epi-PGF, through known and novel pathways of PGF metabolism. The analytical characterization of these products may serve as a basis for identifying the most significant products formed in vivo.

Original languageEnglish
Pages (from-to)495-509
Number of pages15
JournalJournal of Lipid Research
Volume43
Issue number3
Publication statusPublished - 2002

Keywords

  • Gas chromatography-mass spectrometry
  • High performance liquid chromatography-electrospray-tandem mass spectrometry
  • Isolated rat hepatocytes
  • PGF
  • Taurine conjugation

ASJC Scopus subject areas

  • Endocrinology

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