TY - JOUR
T1 - Identification of metabolites from type III F2-isoprostane diastereoisomers by mass spectrometry
AU - Chiabrando, Chiara
AU - Rivalta, Claudia
AU - Bagnati, Renzo
AU - Valagussa, Anna
AU - Durand, Thierry
AU - Guy, Alexandre
AU - Villa, Pia
AU - Rossi, Jean Claude
AU - Fanelli, Roberto
PY - 2002
Y1 - 2002
N2 - 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 PGF2α, 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 PGF2α. 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. PGF2α 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 PGF2α and its metabolites. Of the eight F2-iP diastereoisomers, some were processed similarly to PGF2α, 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-PGF2α, through known and novel pathways of PGF2α metabolism. The analytical characterization of these products may serve as a basis for identifying the most significant products formed in vivo.
AB - 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 PGF2α, 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 PGF2α. 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. PGF2α 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 PGF2α and its metabolites. Of the eight F2-iP diastereoisomers, some were processed similarly to PGF2α, 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-PGF2α, through known and novel pathways of PGF2α metabolism. The analytical characterization of these products may serve as a basis for identifying the most significant products formed in vivo.
KW - Gas chromatography-mass spectrometry
KW - High performance liquid chromatography-electrospray-tandem mass spectrometry
KW - Isolated rat hepatocytes
KW - PGF
KW - Taurine conjugation
UR - http://www.scopus.com/inward/record.url?scp=0036208172&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036208172&partnerID=8YFLogxK
M3 - Article
C2 - 11893786
AN - SCOPUS:0036208172
VL - 43
SP - 495
EP - 509
JO - Journal of Lipid Research
JF - Journal of Lipid Research
SN - 0022-2275
IS - 3
ER -