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pubmed-article:9520386pubmed:abstractTextIsoprostanes are prostaglandin isomers produced from arachidonic acid by a free radical-catalyzed mechanism. Urinary excretion of 8-iso-prostaglandin F2alpha, an isomer of the PGG/H synthase (cyclooxygenase or COX) enzyme product, prostaglandin F2alpha (PGF2alpha), has exhibited promise as an index of oxidant stress in vivo. We have developed a quantitative method to measure isoprostane F2alpha-I, (IPF2alpha-I) a class I isomer (8-iso-PGF2alpha is class IV), using gas chromatography/mass spectrometry. IPF2alpha-I is severalfold as abundant in human urine as 8-iso-PGF2alpha, with mean values of 737 +/- 20.6 pg/mg creatinine. Both isoprostanes are formed in a free radical-dependent manner in low density lipoprotein oxidized by copper in vitro. However, IPF2alpha-I, unlike 8-iso-PGF2alpha, is not formed in a COX-dependent manner by platelets activated by thrombin or collagen in vitro. Similarly, COX inhibition in vivo has no effect on IPF2alpha-I. Neither serum IPF2alpha-I, an index of cellular capacity to generate the isoprostane, nor urinary excretion of IPF2alpha-I, an index of actual generation in vivo, is depressed by aspirin or indomethacin. In contrast, both serum thromboxane B2 and urinary excretion of its 11-dehydro metabolite are depressed by the COX inhibitors. Although serum 8-iso-PGF2alpha formation is substantially depressed by COX inhibitors, urinary excretion of the compound is unaffected. Urinary IPF2alpha-I is elevated in cigarette smokers compared with controls (1525 +/- 180 versus 740 +/- 40 pg/mg creatinine; P < 0.01) and is highly correlated with urinary 8-iso-PGF2alpha (r = 0.9; P < 0.001). Urinary IPF2alpha-I is a novel index of lipid peroxidation in vivo, which can be measured with precision and sensitivity. It is an abundant F2-isoprostane formed in a free radical- but not COX-dependent manner. Although 8-iso-PGF2alpha may be formed as a minor product of COX, this pathway contributes trivially, if at all, to levels in urine. Urinary excretion of both isoprostanes is elevated in cigarette smokers.lld:pubmed
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pubmed-article:9520386pubmed:authorpubmed-author:FitzGeraldG...lld:pubmed
pubmed-article:9520386pubmed:authorpubmed-author:LawsonJ AJAlld:pubmed
pubmed-article:9520386pubmed:authorpubmed-author:RokachJJlld:pubmed
pubmed-article:9520386pubmed:authorpubmed-author:HwangS WSWlld:pubmed
pubmed-article:9520386pubmed:authorpubmed-author:IulianoLLlld:pubmed
pubmed-article:9520386pubmed:authorpubmed-author:PraticòDDlld:pubmed
pubmed-article:9520386pubmed:authorpubmed-author:KhanapureS...lld:pubmed
pubmed-article:9520386pubmed:authorpubmed-author:BarryO POPlld:pubmed
pubmed-article:9520386pubmed:authorpubmed-author:AdiyamanMMlld:pubmed
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pubmed-article:9520386pubmed:pagination3449-54lld:pubmed
pubmed-article:9520386pubmed:dateRevised2009-11-18lld:pubmed
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pubmed-article:9520386pubmed:year1998lld:pubmed
pubmed-article:9520386pubmed:articleTitleIPF2alpha-I: an index of lipid peroxidation in humans.lld:pubmed
pubmed-article:9520386pubmed:affiliationCenter for Experimental Therapeutics, University of Pennsylvania, Philadelphia, PA 19104-6100, USA.lld:pubmed
pubmed-article:9520386pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:9520386pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
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