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.
Georgetown University Medical School, Department of Pharmacology, Rockville, MD 20850.
J
J
Ruiz-Cabello
W C
WC
Buss
S W
SW
Collier
R I
RI
Glazer
J S
JS
Cohen
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