Organic Solvent‐Induced Proximal Tubular Cell Toxicity via Caspase‐3 Activation

Abstract

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.

Keywords :

• Toluene
• Xylene
• Apoptosis
• Caspase‐3
• Proximal tubular cells