31P-NMR spectroscopy and ultrastructural studies on nephrotoxicity of cyclosporine A

Nephrotoxicity of Cyclosporine A in the Rat

“…The light absorbance of the collect ing duct cells of the inner stripe of the outer medulla was chosen as the reference unit, be cause this region appeared to be least affected by cyclosporine A treatment, and cultured collecting duct cells have been shown to be less sensitive to the drug than cells of proximal tubular origin [19]. The measured absorbance values represent intermediate values, since the collecting ducts are composed of different cell types [20], The intense staining for succi nate dehydrogenase activity, chosen for opti mal identification of the different nephron segments, yields absolute absorbance values around or slightly above 1.0, representing the upper limit of optimal measuring conditions [17]These slight methodological limitations may account for the finding of small differ ences in the distribution pattern of succinate dehydrogenase activity, as seen between Sprague-Dawley rats used in this study and Wistar rats, as described previously [17], Such small differences may explain the discrepancy between the present finding of normal en zyme activity in proximal tubules of cyclospo rine-A-treated animals and the detection, made by electron microscopical investigation, of a compensatorily increased number of mi tochondria and cristae membranes in tubules with normal appearance in the neighbour hood of others containing mitochondria with signs of degeneration [21],…”