Cyclooxygenase 1-dependent production of F2-isoprostane and changes in redox status during warm renal ischemia-reperfusion.
The detrimental role of oxidative stress has been widely described in tissue damage caused by ischemia-reperfusion. A nonenzymatic, reactive oxygen species-related pathway has been suggested to produce 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)), an epimer of prostaglandin F(2alpha) (PGF(2alpha)), which has been proposed as an indicator of oxidative stress. Using an in vivo ischemia-reperfusion model in rat kidneys, we investigated intrarenal accumulation of 8-iso-PGF(2alpha) and PGF(2alpha). Both prostanoids accumulated in the ischemic kidney and disappeared upon reperfusion. In addition, a nonselective (acetylsalicylic acid) or selective cyclooxygenase (COX) 1 inhibitor (SC-560) completely abrogated the 8-iso-PGF(2alpha) and PGF(2alpha) formation in kidneys subjected to ischemia. COX2 inhibition had no effect on the production of these prostanoids. Therefore the two metabolites of arachidonic acid seemed to be produced via an enzymatic COX1-dependent pathway. Neither COX overexpression nor COX activation was detected. We also investigated renal glutathione, which is considered to be the major thiol-disulfide redox buffer of the tissue. Total and oxidized glutathione was decreased during the ischemic period, whereas no further decrease was seen for up to 60 min of reperfusion. These data demonstrate that a dramatic decrease in antioxidant defense was initiated during warm renal ischemia, whereas the 8-iso-PGF(2alpha) was related only to arachidonate conversion by COX1.
Favreau
Frederic
F
INSERM ERM 324, Ischémie-Reperfusion en Transplantation Rénale, Faculté de Médecine et de Pharmacie, IFR59, Université de Poitiers, and Laboratoire de Biochimie et Toxicologie, CHU de Poitiers, BP 577, 86021 Poitiers, France.
Petit-Paris
Isabelle
I
Hauet
Thierry
T
Dutheil
Delphine
D
Papet
Yves
Y
Mauco
Gerard
G
Tallineau
Claude
C
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D051545:Cyclooxygenase 1; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D028441:F2-Isoprostanes / Q000737:chemistry*; D005609:Free Radicals; D008401:Gas Chromatography-Mass Spectrometry; D005978:Glutathione / Q000378:metabolism; D007511:Ischemia; D007527:Isoenzymes / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D004791:Enzyme Inhibitors; D028441:F2-Isoprostanes; D005609:Free Radicals; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C115461:SC 560; C075750:8-epi-prostaglandin F2alpha; D016718:Arachidonic Acid; D015237:Dinoprost; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D005978:Glutathione