Role of lipid peroxidation in H2O2-induced renal epithelial (LLC-PK1) cell injury.
The exact sequence of events or mechanisms by which H2O2 induces renal cell injury remains undetermined. Specifically, whether the attendant lipid peroxidation is a cause or an effect remains unclear. Employing H2O2 and LLC-PK1 cells, we tested the hypothesis that lipid peroxidation is a seminal event and that its inhibition is cytoprotective. In a time course study, lipid peroxidation (thiobarbituric acid reaction) and degradation (release of [3H]arachidonic acid) preceded H2O2-induced cytolysis (51Cr and lactate dehydrogenase release). The role of preceding lipid peroxidation in cytolysis was examined with lipid radical scavengers. alpha-Tocopherol and lazaroid compound 2-methyl aminochroman dose-dependently inhibited H2O2-induced lipid peroxidation and prevented cytolysis. 2-Methyl aminochroman cytoprotection was associated with blockade of lipid degradation. 21-Aminosteroid, another lazaroid, also inhibited lipid peroxidation and prevented cytolysis. These findings provide evidence that lipid alterations contribute to H2O2-mediated LLC-PK1 injury and, for the first time, demonstrate the potency of lazaroids in a renal cell line. In vivo studies with lazaroids may define the role of lipid peroxidation in acute renal injury models.
Department of Medicine, University of Mississippi Medical Center, Jackson 39216-4505.
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Salahudeen
D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000032:analysis; D002374:Catalase / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D002860:Chromium Radioisotopes; D004137:Dinitrochlorobenzene / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007687:Kidney Tubules, Proximal; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D018374:LLC-PK1 Cells; D015227:Lipid Peroxidation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D013552:Swine; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013997:Time Factors; D014316:Tritium
D002839:Chromans; D002860:Chromium Radioisotopes; D004137:Dinitrochlorobenzene; D010879:Piperazines; D017392:Thiobarbituric Acid Reactive Substances; D014316:Tritium; C066382:U 78517F; D016718:Arachidonic Acid; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D000640:Amitrole