Organic solvent-induced proximal tubular cell toxicity via caspase-3 activation.


BACKGROUND Occupational exposure to solvents may be associated with development and progression of tubulo-interstitial fibrosis and chronic renal failure. However, the cellular mechanisms by which this occurs remain elusive. MATERIALS AND METHODS The cytotoxicity of proximal tubular cells (LLC-PK1) exposed to 106 mg/mL of p-xylene or 92 mg/mL of toluene was compared with untreated controls using cell viability (MTS assay) and caspase-3 activity, with or without caspase-3 selective inhibitor. RESULTS Both compounds reduced cell viability and increased caspase-3 activation (P < 0.005). Inhibition of caspase-3 by the selective inhibitor DEVD-CHO prevented injury (P < 0.001) and inhibited solvent-induced caspase-3 activation (P < 0.005). CONCLUSION Inhibition of caspase-3, the critical caspase in the apoptosis process, prevents cell injury in LLC-PK1. This suggests that caspase-3 may play a pivotal role in solvent-induced proximal tubular cell injury.

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@article{AlGhamdi2003OrganicSP, title={Organic solvent-induced proximal tubular cell toxicity via caspase-3 activation.}, author={Saeed Saeed Al-Ghamdi and Martin J. Raftery and Muhammad Yaqoob}, journal={Journal of toxicology. Clinical toxicology}, year={2003}, volume={41 7}, pages={941-5} }