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 < 0.00 1) 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-PKl This suggests that caspase-3 may play a pivotal role in solvent-induced proximal tubular cell injury.