No 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

No abstract