Role of calcium in cisplatin-induced cell toxicity in rat renal cortical slices.

Abstract The disruption of intracellular Ca 2+ homoeostasis is involved in cisplatin-induced nephrotoxicity. The role of Ca 2+ in cisplatin toxicity was studied by use of rat renal cortical slices. Cisplatin (2 m m ) increased the leakage of aspartate aminotransferase (AST) from 1.4 ± 0.5 units/g wet weight (mean ± SE) with control slices to 3.4 ± 0.5 units/g wet weight. The leakage of lactate dehydrogenase (LDH) was increased from 3.8 ± 1.1 units/g wet weight to 13.7 ± 1.0 units/g wet weight. Pretreatment of slices with ethylene glycol-bis( β -aminoethylether) N , N , N ′ N ′-tetraacetic acid (1 m m ) to buffer intracellular Ca 2+ significantly decreased the cisplatin-induced leakage of these two enzymes to 65% and 53%, respectively, of levels with cisplatin alone. An increase in extracellular Ca 2+ , or omission of Ca 2+ from the medium, had no effect on cisplatin-induced slice toxicity. Furthermore, the Ca 2+ channel blockers nifedipine and diltiazem did not protect against cytotoxicity by cisplatin, although verapamil gave mild protection and decreased the cisplatin-induced release of AST and LDH to 78% and 75%, respectively, of that caused by cisplatin alone. The results suggest that intracellular Ca 2+ is important in cisplatin-induced nephrotoxicity but that disruption of cytosolic Ca 2+ is not caused by opening of Ca 2+ channels of the plasma membrane or even by leakage through the injured membrane.