Adverse effects of oxidative stress on renal cells and its prevention by antioxidants

Background and Purpose: Recent reports suggest that reactive oxygen species ; e.g., hydrogen peroxide (H2O2), could be the primary cause of various dru g-induced renal injuries. We investigated the effects of H2O2 on renal cell s to understand its mode of action and to explore cytoprotection from such a fatal injury. Materials and Methods: Renal proximal tubular LLC-PK1 cells were exposed to various concentrations of H2O2, and cell viability was determined at speci fied times. Lipid peroxidation assay and Western blot analysis of heat shoc k proteins (Hsp70 and Hsp90) were performed to assess the cellular effects. Results: The dose-response study showed that H2O2 greater than or equal to 100 mu M was severely cytotoxic. Even a 1-h exposure was sufficient to indu ce >95% cell death in 24 h, Lipid peroxidation was significantly (>50%) inc reased, while Hsp90, but not Hsp70, was partially degraded, to an similar t o 85-kDa fragment, after a 3-h H2O2 exposure. However, such cytotoxic cell death was remarkably (similar to 90%) prevented by the antioxidants pyruvat e or N-acetylcysteine (NAC), and Hsp90 remained intact. Conclusion: Hydrogen peroxide-induced renal cell death involves increased l ipid peroxidation and partial degradation of Hsp90. Both pyruvate and NAC a re capable of detoxifying H2O2 to maintain cell viability and Hsp90 integri ty. Acute renal injuries associated with oxidative stress might preventable by appropriate antioxidants.