LLC-PK1 cells as a model for renal toxicity caused by arsine exposure

The,mechanisms of arsine (AsH3) toxicity are not completely understood. Studies were undertaken to determine AsH3, and arsenite [As(lll)] toxicity in a renal tubular epithelial cell line to model kidney dysfunction caused by AsH3, exposure. The hypothesis was that As(III) is the toxic metabolite responsible for the renal toxicity of AsH3,. There was a concentration- and time-dependent toxic response after As(III) incubation. As(III) produced significant LDH leakage as early as 1 h and intracellular potassium loss at 5 h. AsH3, produced no changer in these parameters. AsH3, affected neither potassium nor LDH levels over 24 h and up to I mM AsH3, concentration. In this system, As(III) induced LDH leakage before K+ loss. Oxidative stress-like toxicity effects were also studied by determining levels of glutathione (GSH), glutathione disulfide (GSSG), and heat-shock protein 32 (Hsp32) levels. GSH levels were not markedly affect ed by any arsenical over a 6-h period or UP to 100 mu M concentration of the arsenical. However, 100 CIM AsH3, significantly increased GSSG levels as early as 30 min and reached a maximum at 2.5 h. Incubation with 10 mu M AsH3, was sufficient to significantly increase GSSG levels. As(lll) had no marked effect on GSSC. Both arsenicals (50 mu M) produced a slight increase (about threefold) in Hsp32 levels after 4-h incubation. These results showed that unchanged Ast-l, produced oxidative stress-like toxic effects without producing cell death. However, similar As(III) concentrations induced the stress response and were toxic to the cells. These data indicated that AsH3, is not directly toxic to LLC-PK1 cells.