Intracellular Localization of Cyclosporin A in the Rat Kidney
Cyclosporin A (CyA), a most potent and clinically useful immuno-suppres-sive agent, also produces a number of side-effects in man and experimental animals. Nephrotoxicity, characterised by the formation of numerous large vacuoles in the straight proximal tubules in the corticomedullary region or the S3 (P3) segment of the nephron (1), is the most notable side effect of CyA. There are indications that the S3 region may also accumulate the greatest proportion of CyA (2). The biochemical changes associated with the nephrotoxicity are consistent with tubular damage and include elevated urinary excretion of lysosomal and brush border enzymes (3). The hetero-geneous range of vacuoles appear to be of lysosomal, mitochondrial and possibly of endoplasmic reticulum origin. However, the positive localiz-ation of acid phosphatase within many of the vacuoles (4) suggest that the majority might be of lysosomal origin. What remains unknown is whether these vacuoles form as a result of accumulation of cyclosporin or as an indirect effect of more complex secondary factors. The aim of the study described here was to investigate the intracellular localization of CyA in the kidney and to determine whether the vacuoles accumulate and contain CyA.
KeywordsSucrose Sedimentation Fractionation Cyclosporin Cytosol
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