J. Ruizcabello et al., CHANGES IN ATP AFTER CYCLOSPORINE-A TREATMENT IN A RENAL EPITHELIAL-CELL LINE IN THE RAT STUDIED BY P-31-NMR, Research communications in molecular pathology and pharmacology, 86(1), 1994, pp. 3-13
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.