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Communication Dans Un Congrès Année : 2023

Identification and Characterization of Novel F2-Isoprostane Metabolites

Résumé

F2-isoprostanes (F2-IsoPs) are formed from the free radical oxidation of arachidonic acid and are widely used as biomarkers of endogenous oxidative damage. Sixty-four F2-IsoP isomers are generated during lipid peroxidation; however, most studies have focused only on one isomer, 15-F2t-IsoP (commonly referred to as 8-iso-PGF2α). Immunoassay and mass spectrometric (MS) techniques have been developed to quantify 15-F2t-IsoP in biological fluids. Even though this molecule has a short half-life of only a few minutes, most studies quantify 15-F2t-IsoP directly rather than its’ urinary metabolite (2,3-dinor-5,6-dihydro-15-F2tIsoP, 15-F2t-IsoP-M). An increasing body of evidence demonstrates the efficacy of 15-F2t-IsoP-M quantification. For example, 15-F2t-IsoP-M, but not 15-F2t-IsoP, was positively associated with age and postmenopausal status in a large population study of middle-aged and older women. Urinary 15-F2tIsoP-M also shows associations with plasma antioxidant levels, carbohydrate intake, glycemic index, and environmental exposures while urinary 15-F2t-IsoP does not. The utility of 15-F2tIsoP measurement is further limited by the fact that this molecule can also be generated enzymatically via the cyclooxygenases. On the other hand, 5-series F2-IsoPs are only generated via nonenzymatic mechanisms. And, it has been demonstrated that these molecules are present in greater abundance in plasma, tissue, and urine than 15-series F2-IsoPs. Yet, 5-series F2-IsoP metabolism remains unexplored. We have thus undertaken experiments to identify and characterize metabolites of 5-epi-5-F2t-IsoP and 5-epi- 5-F2c-IsoP, two abundantly produced 5-series F2-IsoPs, in human liver microsomes. Using targeted and untargeted metabolomic approaches, glucuronide and sulfate metabolites of F2-IsoPs have been identified by MS. Metabolism of these molecules by specific enzymes has also been tested. Collectively, these findings indicate that F2-IsoP metabolism is more complex than previously appreciated. The presence of these metabolites in human urine is under investigation. We anticipate that the completion of this work will redefine F2-IsoP metabolism and outline a strategy to comprehensively evaluate endogenous formation of these important molecules
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Dates et versions

hal-04292105 , version 1 (17-11-2023)

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Citer

Ginger Milne, Marina Nogueira, Stephanie Sanchez, Benlian Gao, Warda Amin, et al.. Identification and Characterization of Novel F2-Isoprostane Metabolites. SfRBM-SFRRI 2023, Nov 2023, Punta del Este, Uruguay. pp.S72, ⟨10.1016/j.freeradbiomed.2023.10.161⟩. ⟨hal-04292105⟩
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