Biomarkers of oxidative stress study III. Effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in CCl4 poisoning.

Kadiiska MB, Gladen BC, Baird DD, Graham LB, Parker CE, Ames BN, Basu S, Fitzgerald GA, Lawson JA, Marnett LJ, Morrow JD, Murray DM, Plastaras J, Roberts LJ, Rokach J, Shigenaga MK, Sun J, Walter PB, Tomer KB, Barrett JC, Mason RP
Free Radic Biol Med. 2005 38 (6): 711-8

PMID: 15721981 · 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.

MeSH Terms (23)

Animals Anti-Inflammatory Agents, Non-Steroidal Biomarkers Carbon Tetrachloride Carbon Tetrachloride Poisoning Chromatography, High Pressure Liquid Free Radicals Gas Chromatography-Mass Spectrometry Immunoassay Indomethacin Inflammation Lipid Metabolism Lipid Peroxidation Mass Spectrometry Meclofenamic Acid Oxidative Stress Oxygen Prostaglandins Protein Isoforms Rats Rats, Inbred F344 Thromboxane A2 Time Factors

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