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 F2α (8-iso-PGF2α), an epimer of prostaglandin F2α (PGF2α), 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-PGF2α and PGF2α. 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-PGF2α and PGF2α 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-PGF2α was related only to arachidonate conversion by COX1.