Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Cyclooxygenase 1-dependent production of F2-isoprostane and changes in redox status during warm renal ischemia-reperfusion. 1505 44

PGF(2)-like compounds are formed in abundance in vivo by the free radical-induced peroxidation of arachidonic acid, independent of the cyclooxygenase enzyme. These compounds are collectively referred to as F(2)-isoprostanes because of their structural similarity to cyclooxygenase-derived PGF(2alpha). Certain findings suggest a potential role for isoprostanes as mediators of some of the adverse sequelae of ischemia-reperfusion injury to kidney. Recent evidence also suggests a potentially important role for isoprostanes in the pathogenesis of hepatorenal syndrome. Cell culture studies suggest that cisplatin-induced LLC-PK1 cell injury may be attended by increased isoprostane production through a mechanism involving thiol depletion. Another area in which a role for free radical-induced lipid peroxidation and F(2)-isoprostanes has been suggested is in the pathogenesis of ciclosporin (CSA)-induced renal toxicity. A recent study also suggests that enhanced formation renal F(2)-isoprostanes may be relevant to the progressive reduction in renal blood flow demonstrable in aging kidneys. This emerging evidence suggests that further studies are warranted to determine the importance of F(2)-isoprostanes in human renal diseases characterized by renal vasoconstriction, such as renal ischemia, hepatorenal syndrome, renal senescence and toxic nephropathies.
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PMID:F2-isoprostanes and the kidney. 1561 48