期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：7
页码：3449-3454
DOI：10.1073/pnas.95.7.3449
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Isoprostanes are prostaglandin isomers produced from arachidonic acid by a free radical-catalyzed mechanism. Urinary excretion of 8-iso-prostaglandin F2, an isomer of the PGG/H synthase (cyclooxygenase or COX) enzyme product, prostaglandin F2 (PGF2), has exhibited promise as an index of oxidant stress in vivo. We have developed a quantitative method to measure isoprostane F2-I, (IPF2-I) a class I isomer (8-iso-PGF2 is class IV), using gas chromatography/mass spectrometry. IPF2-I is severalfold as abundant in human urine as 8-iso-PGF2, 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, IPF2-I, unlike 8-iso-PGF2, 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 IPF2-I. Neither serum IPF2-I, an index of cellular capacity to generate the isoprostane, nor urinary excretion of IPF2-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-PGF2 formation is substantially depressed by COX inhibitors, urinary excretion of the compound is unaffected. Urinary IPF2-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-PGF2 (r = 0.9; P < 0.001). Urinary IPF2-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-PGF2 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.
