Oxidized derivatives of ω-3 fatty acids: identification of IPF3α-VI in human urine

Abstract

Isoprostanes (iPs) are prostaglandin-like molecules derived from autoxidation of polyunsaturated fatty acids (PUFAs). Urinary iP levels have been used as indices of in vivo lipid peroxidation. Thus far, it has only been possible to measure iPs derived from arachidonic acid in urine, because levels of iPs/neuroprostanes (nPs) derived from v3-PUFAs have been found to be below detection limits of available assays. Because of the interest in v3-PUFA dietary supplementation, we developed specific methods to measure nPF 4a -VI and iPF 3a -VI [derived from 4,7,10,13,16,19-docosahexaenoic acid (DHA) and 5,8,11,14,17-eicosapentaenoic acid (EPA)] using a combination of chemical synthesis, gas chromatography/mass spectrometry (GC/MS), and liquid chromatography tandem mass spectrometry (LC/MS/MS). Although nPF 4a -VI was below the detection limit of the assay, we conclusively identified iPF 3a -VI in human urine by GC/MS and LC/MS/MS. The mean levels in 26 subjects were z300 pg/mg creatinine. Our failure to detect nPF 4a -VI may have been due to its rapid metabolism by b-oxidation to iPF 3a -VI, which we showed to occur in rat liver homogenates. In contrast, iPF 3a -VI is highly resistant to b-oxidation in vitro. Thus iPF 3a -VI can be formed by two mechanisms: i) direct autoxidation of EPA, and ii) b-oxidation of nPF 4a -VI, formed by autoxidation of DHA. This iP may therefore serve as an excellent marker for the combined in vivo peroxidation of EPA and DHA.-Lawson, J. A., S. Kim, W. S. Powell, G. A. FitzGerald, and J. Rokach. Oxidized derivatives of v-3 fatty acids: identification of IPF 3a -VI in human urine. J. Lipid Res. 2006Res. . 47: 2515Res. -2524

Novel Eicosapentaenoic Acid-derived F3-isoprostanes as Biomarkers of Lipid Peroxidation

“…While F 2 -iPs and F 3 -iPs are excreted into urine in their original form, the F 4 -iPs formed from DHA ( Fig. 1) are at least partly metabolized to F 3 -iPs before excretion (20,24). Given the potential utility of noninvasive biomarkers of EPA and DHA peroxidation and our previous work with F 2 -iPs (25,26), we sought to determine whether members of group VI (Fig.…”

Quantification of urinary F2-isoprostanes with 4(RS)-F4t-neuroprostane as an internal standard using gas chromatography–mass spectrometry

“…To our knowledge, there are no literature reports of NeuroPs in human urine. Lawson et al [32] were unable to detect nPF4a-VI in urine sample from healthy subjects (n = 20) by LC/MS/MS. Furthermore, measurement by Montine et al [33] in Alzheimer disease (AD) patients of urine NeuroP by GC-NICI-MS were below the limit of detection, NeuroP are elevated in diseased region of brain and CSF from patients with advanced AD.…”

Beyond Prostaglandins—Chemistry and Biology of Cyclic Oxygenated Metabolites Formed by Free‐Radical Pathways from Polyunsaturated Fatty Acids

“…The diastereoselectivity of the 5-exo radical cyclizations is also sensitive to the protecting group pattern, and proceeds from 234 to the oxabicyclo[3. [15c, 105c, 109] In 1994 Renaud and Vionnet reported the total synthesis of 15-F 2c -IsoP (15-2 b) in which they used a convergent pathway starting from (AE )-7-oxabicyclo[2.2.1]hept-5-en-2-one (240). [242] A sequence of group-transfer radical addition of phenylselenylmalonate and acyl migration under irradiation led to the rearranged product 241 (Scheme 68).…”