Abstract
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.
Original language | English (US) |
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Pages (from-to) | F30-F38 |
Journal | American Journal of Physiology - Renal Physiology |
Volume | 268 |
Issue number | 1 |
State | Published - 1994 |
Keywords
- 2-methyl aminochroman
- 21-aminosteroid
- Arachidonic acid release
- Cell membrane
- In vitro
- Kidney
- Lazaroids
- Oxidant injury
- Reactive oxygen species
ASJC Scopus subject areas
- Physiology
- Urology