Saeed S Al-Ghamdi1, Martin J Raftery, Muhammad M Yaqoob. 1. Department of Experimental Medicine and Nephrology, St. Bart's and Royal London School of Medicine and Dentistry, Queen Mary-University of London, London, UK. s_alghamdi@go.com
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.
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.