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F2 isoprostanes (F2-iPs) are thought to arise from the free radical-mediated peroxidation of phospholipid-bound arachidonic acid.1 They are cleaved, presumably by an unidentified phospholipase A2, and are found in the circulation and the urine. 8,12-iso-iPF2α-VI-1,5-lactone is a racemic mixture of the lactone forms of the free acid, 8,12-iso- iPF2α-VI. Previously called IPF2α -I,2 the free acid form, iPF2α-VI, is the most abundant F2-iP regioisomer measured in the urine of rats treated with CCl4 to induce lipid peroxidation.3 iPF2α-VI is the only regioisomer that undergoes lactonization, and this occurs slowly in vivo or can be driven chemically.4 The less polar lactone is readily separated from the free acid forms of iPF2α.4 While the level of iPF2α-VI in plasma, urine and organs is used as a biomarker for oxidative stress,5,6 some F2-iPs also evoke significant biological effects.7 It is not known if 8,12-iso-iPF2α-VI-1,5-lactone has important physiological effects.
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1
Lawson, J.A., Li, H., Rokach, J., et al. Identification of two major F2 isoprostanes, 8,12-iso- and 5-epi-8,12-iso-isoprostane F2α-VI, in human urine. J Biol Chem 273 29295-29301 (1998).
2
Morrow, J.D., Hill, K.E., Burk, R.F., et al. A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci USA 87 9383-9387 (1990).
3
Waugh, R.J., Morrow, J.D., Roberts, L.J., et al. Identification and relative quantitation of F2-isoprostane regioisomers formed in vivo in the rat. Free Radic Biol Med 23 943-954 (1997).
4
Adiyaman, M., Lawson, J.A., Khanapure, S.P., et al. Total synthesis of 17,17,18,18-d4-iPF2a-VI and quantification of iPF2a-VI in human urine by gas chromatography/mass spectrometry. Anal Biochem 262 45-56 (1998).
5
Practico, D., Barry, O.P., Lawson, J.A., et al. IPF2a-I: An index of lipid peroxidation in humans. Proc Natl Acad Sci USA 95 3449-3454 (1998).
6
Van Eck, M., Hoekstra, M., Hildebrand, R.B., et al. Increased oxidative stress in scavenger receptor BI knockout mice with dysfunctional HDL. Arterioscler Thromb Vasc Biol 27 2413-2419 (2007).
7
Gardi, C., Arezzini, B., Monaco, B., et al. F2-isoprostane receptors on hepatic stellate cells. Lab Invest 88 124-131 (2008).
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