Kadiiska M B, Gladen B C, Baird D D, Graham L B, Parker C E, Ames B N, Basu S, Fitzgerald G A, Lawson J A, Marnett L J, Morrow J D, Murray D M, Plastaras J, Roberts L J, Rokach J, Shigenaga M K, Sun J, Walter P B, Tomer K B, Barrett J C, Mason R P
National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA.
Free Radic Biol Med. 2005 Mar 15;38(6):711-8. doi: 10.1016/j.freeradbiomed.2004.10.024.
Plasma and urinary levels of malondialdehyde-like products (MDA) and isoprostanes were identified as markers of in vivo lipid peroxidation in an animal model of CCl4 poisoning. We sought to determine the extent to which the formation of these oxidation products is influenced by inhibition of the cyclooxygenase enzymes which catalytically generate proinflammatory lipid peroxidation products known as prostaglandins and thromboxane. In the present studies, after induction of oxidant stress in rats with CCl4, lipid peroxidation products measured in plasma and urine demonstrate that isoprostanes and MDA can be partially inhibited by cyclooxygenase inhibitors, albeit to different extents. The lowering of isoprostane and MDA formation, however, may not to due primarily to the diminution of catalytic generation of isoprostanes or MDA by the cyclooxygenases but, rather, may be the result of the suppression of nonenzymatic lipid peroxidation. This is suggested since 8,12-iso-iPF2alpha-VI is also reduced by indomethacin, yet, unlike other isoprostanes and MDA, it is not generated catalytically by the cyclooxygenase. Thus, although the two cyclooxygenase inhibitors we tested have statistically significant effects on the measurements of both isoprostanes and MDA in this study, the results provide evidence that these lipid-degradation products primarily constitute markers of oxidative stress.
在四氯化碳中毒动物模型中，血浆和尿液中的丙二醛样产物（MDA）和异前列腺素被确定为体内脂质过氧化的标志物。我们试图确定这些氧化产物的形成在多大程度上受到环氧化酶抑制的影响，环氧化酶催化生成促炎性脂质过氧化产物，即前列腺素和血栓素。在本研究中，用四氯化碳诱导大鼠氧化应激后，血浆和尿液中测量的脂质过氧化产物表明，异前列腺素和MDA可被环氧化酶抑制剂部分抑制，尽管程度不同。然而，异前列腺素和MDA形成的降低可能主要不是由于环氧化酶催化生成异前列腺素或MDA的减少，而是非酶促脂质过氧化受到抑制的结果。这一点得到了提示，因为吲哚美辛也能降低8,12-异-iPF2α-VI，但与其他异前列腺素和MDA不同，它不是由环氧化酶催化生成的。因此，尽管我们测试的两种环氧化酶抑制剂在本研究中对异前列腺素和MDA的测量有统计学上的显著影响，但结果提供了证据，表明这些脂质降解产物主要构成氧化应激的标志物。
