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 H₂C₂-induced cytolysis (⁵¹Cr and lactate dehydrogenase release). The role of preceding lipid peroxidation in cytolysis was examined with lipid radical scavengers. α-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.