4 research outputs found

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

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    F 2 -isoprostanes (F 2 -iPs) are prostaglandin (PG)-like products of non-enzymatic free radical-catalyzed peroxida- tion of arachidonic acid that are now widely used as indices of lipid peroxidation in vivo. Knowledge of the metabolic fate of F 2 -iPs in vivo is still scant, despite its importance for defining their overall formation and biological effects in vivo. Type III F 2 -iPs, which are diastereoisomers of cyclo- oxygenase-derived PGF 2 a , may be metabolized through the pathways of PG metabolism. We therefore studied the in vitro metabolism of eight synthetic Type III F 2 -iP diastereo- isomers in comparison with PGF 2 a . We used gas chroma- tography-mass spectrometry and high performance liquid chromatography-electrospray-tandem mass spectrometry for structural identification of metabolites formed after in- cubation of the various compounds with isolated rat hepato- cytes. PGF 2 a was metabolized to several known products, resulting from a combination of b -oxidation, reduction of D 5 and/or D 13 double bonds, and 15-OH oxidation, plus other novel products deriving from conjugation with tau- rine of PGF 2 a and its metabolites. Of the eight F 2 -iP diaste- reoisomers, some were processed similarly to PGF 2 a , whereas others showed peculiar metabolic profiles according to spe- cific stereochemical configurations. These data represent the first evidence of biodegradation of selected Type III F 2 -iP isomers other than 8- epi- PGF 2 a , through known and novel pathways of PGF 2 a metabolism. The analytical characterization of these products may serve as a basis for identifying the most significant products formed in vivo. — Chiabrando, C., C. Rivalta, R. Bagnati, A. Valagussa, T. Durand, A. Guy, P. Villa, J-C. Rossi, and R. Fanelli. Identifi- cation of metabolites from Type III F 2 -isoprostane diastereo- isomers by mass spectrometry. J. Lipid Res. 2002. 43: 495-509

    Long-term vitamin E supplementation fails to reduce lipid peroxidation in people at cardiovascular risk: analysis of underlying factors

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    BACKGROUND: Antioxidant supplementation with vitamin E had no effect in the prevention of cardiovascular diseases (CVD) in three recent large, randomized clinical trials. In order to reassess critically the role of vitamin E in CVD prevention, it is important to establish whether these results are related to a lack of antioxidant action. METHODS: We examined the in vivo antioxidant effect of vitamin E (300 mg/day for about three years) in 144 participants in the Primary Prevention Project (females and males, aged ≥ 50 y, with at least one major CV risk factor, but no history of CVD). Urinary 8-epi-PGF(2α) (isoprostane F(2α)-III or 15-F(2t)-isoP), a validated biomarker of lipid peroxidation, was measured by mass spectrometry. RESULTS: Urinary excretion of 8-epi-PGF(2α) [pg/mg creatinine, median (range)] was 141 (67–498) in treated and 148 (76–561) in untreated subjects (p = 0.10). Taking into account possible confounding variables, multiple regression analysis confirmed that vitamin E had no significant effect on this biomarker. Levels of 8-epi-PGF(2α) were in the normal range for most subjects, except smokers and those with uncontrolled blood pressure or hyperglycemia. CONCLUSIONS: Prolonged vitamin E supplementation did not reduce lipid peroxidation in subjects with major cardiovascular risk factors. The observation that the rate of lipid peroxidation was near normal in a large proportion of subjects may help explain why vitamin E was not effective as an antioxidant in the PPP study and was ineffective for CVD prevention in large scale trials
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