Toxicology in vitro : an international journal published in association with BIBRA
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The cytoprotection of LLC-PK1 cells afforded by endoplasmic reticulum (ER) stress preconditioning suggests that the ER plays an important role during drug-induced renal toxicity. However, in vitro studies have been largely limited to LLC-PK1 cells and model toxins. Therefore, we tested the hypothesis that cytoprotection following ER stress preconditioning is a common property of renal cell lines (LLC-PK1 (pig), NRK-52E (rat), HEK293 (human), MDCK (dog)) and extends to clinically relevant nephrotoxins. ⋯ Toxicity of clinically relevant drugs (cisplatin, gentamicin, glyoxylate, cyclosporine A, p-aminophenol) was significantly decreased in cells preconditioned by tunicamycin or DTTox. These results demonstrate that ER stress preconditioning offers cytoprotection against clinically relevant nephrotoxins in renal cell lines from multiple species, although there were qualitative and quantitative differences between the cell lines. These results support the hypothesis that ER is involved in drug-induced renal toxicity.