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.
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.
Kadiiska
M B
MB
National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, USA. Kadiiska@niehs.nih.gov
Gladen
B C
BC
Baird
D D
DD
Graham
L B
LB
Parker
C E
CE
Ames
B N
BN
Basu
S
S
Fitzgerald
G A
GA
Lawson
J A
JA
Marnett
L J
LJ
Morrow
J D
JD
Murray
D M
DM
Plastaras
J
J
Roberts
L J
LJ
Rokach
J
J
Shigenaga
M K
MK
Sun
J
J
Walter
P B
PB
Tomer
K B
KB
Barrett
J C
JC
Mason
R P
RP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid; D005609:Free Radicals; D008401:Gas Chromatography-Mass Spectrometry; D007118:Immunoassay; D007213:Indomethacin / Q000378:metabolism / Q000494:pharmacology*; D007249:Inflammation; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D013058:Mass Spectrometry; D008469:Meclofenamic Acid / Q000494:pharmacology*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D020033:Protein Isoforms; D051381:Rats; D011916:Rats, Inbred F344; D013928:Thromboxane A2 / Q000378:metabolism; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D005609:Free Radicals; D011453:Prostaglandins; D020033:Protein Isoforms; D008469:Meclofenamic Acid; D013928:Thromboxane A2; D002251:Carbon Tetrachloride; D010100:Oxygen; D007213:Indomethacin