title: Effect of arachidonic acid metabolic inhibitors on hypoxia/reoxygenation-induced renal cell injury.
abstract: The present study was undertaken to examine the role of arachidonic acid (AA) metabolites in hypoxia/reoxygenation (H/R)-induced renal cell injury in rabbit renal cortical slices using AA metabolic inhibitors. Inhibitors of cyclooxygenase (indomethacin and diclofenac sodium) and lipoxygenase pathways (nordihydroguaiaretic acid, caffeic acid, and eicosapentaenoic acid) reduced H/R-induced LDH release in a dose-dependent manner, whereas an inhibitor of cytochrome P-450 monooxygenase pathway ethoxyresorufin was not effective. AA increased LDH release in control slices, and the effect was not altered by indomethacin and nordihydroguaiaretic acid. The protective effect of indomethacin was not affected by addition of PGE2, a main product of cyclooxygenase pathway in the kidney. H2O2-induced LDH release was prevented by inhibitors of lipoxygenase but not by inhibitors of cyclooxygenase and cytochrome P-450 monooxygenase H/R-induced LDH release was not altered by iron chelators, phenanthroline and deferoxamine, and a potent antioxidant, N,N'-diphenyl-p-phenylenediamine, suggesting that the H/R-induced cell injury is not attributed to a generation of reactive oxygen species. Morphological studies showed that H/R-induced structural changes including cell necrosis were significantly prevented by indomethacin. These results suggest that inhibitors of cyclooxygenase and lipoxygenase pathways exert a direct protective effect against the H/R-induced cell injury in renal tubules. Whether these effects are mediated by alterations of AA metabolic pathways is not certain.
authors.affiliation: Department of Physiology, College of Medicine, Pusan National University, Korea. Kim430@hyowon.cc.pusan.kr
authors.forename: Y K
authors.initials: YK
authors.lastname: Kim
authors.forename: M Y
authors.initials: MY
authors.lastname: Hwang
authors.forename: J S
authors.initials: JS
authors.lastname: Woo
authors.forename: J S
authors.initials: JS
authors.lastname: Jung
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007502:Iron Chelating Agents / Q000494:pharmacology; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000975:Antioxidants; D016861:Cyclooxygenase Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D007502:Iron Chelating Agents; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D007770:L-Lactate Dehydrogenase; D015232:Dinoprostone