CHANGES IN ATP AFTER CYCLOSPORINE-A TREATMENT IN A RENAL EPITHELIAL-CELL LINE IN THE RAT STUDIED BY P-31-NMR

Experiments reported in this paper provide evidence that P-31-NMR spec troscopy can detect mitochondrial toxicity produced by cyclosporin A ( CsA) in cultured rat renal cells cast in agarose threads. The effects observed in the normal rat kidney epithelial cell line NRK-52E include dose-dependent increases in the beta-ATP signal at CsA concentrations from 2.5-25 mu g/ml. At a CsA concentration of 100 mu g/ml, there is a severe decrease in the beta-ATP signal with a concomitant increase i n the inorganic phosphate (P-i) signal. Effects observed in NRK-52E ce lls perfused with 100 mu g/ml CsA mimic those previously observed by P -31-NMR spectroscopy using a surface coil over exposed kidneys of rats given chronic oral doses of 5 and 25 mg/kg/day CsA for periods of up to 90 days. These observations support the hypothesis that mitochondri al toxicity contributes to induction of CsA nephrotoxicity.