Changes in ATP after cyclosporin A treatment in a renal epithelial cell line in the rat studied by 31P-NMR spectroscopy.
Experiments reported in this paper provide evidence that 31P-NMR spectroscopy 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 micrograms/ml. At a CsA concentration of 100 micrograms/ml, there is a severe decrease in the beta-ATP signal with a concomitant increase in the inorganic phosphate (P(i)) signal. Effects observed in NRK-52E cells perfused with 100 micrograms/ml CsA mimic those previously observed by 31P-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 mitochondrial toxicity contributes to induction of CsA nephrotoxicity.
Ruiz-Cabello
J
J
Georgetown University Medical School, Department of Pharmacology, Rockville, MD 20850.
Buss
W C
WC
Collier
S W
SW
Glazer
R I
RI
Cohen
J S
JS
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D016572:Cyclosporine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051381:Rats
D016572:Cyclosporine; D000255:Adenosine Triphosphate