ELECTRON MICROSCOPIC OBSERVATION OF THE RENAL TUBULAR DAMAGE AFTER ADMINISTRATION OF CIS-DIAMMINEDICHLOROPLATINUM (II)

Abstract

Nephrotoxicity is the major dose-limiting side effect of Cis-Diamminedichloroplatinum (II) (CDDP) and it develops tubular damage. The mechanism of the damage has not been elucidated clearly. To clarify the mechanism, an experimental pathomorphological study was performed.
Approximately 80 Wistar strain rats weighing 200 to 250g. were submitted to the study. Attention was directed to the damage and the recovery process of the epithelium of the proximal tubules, especially those of the pars recta. Together with the morphological study, biochemical study, determination of Platinum concentration in serum and X-ray microanalysis were also done. The animals were divided into two groups and in one of them, 2, 3, 4, 6, and 10 mg/kg/day CDDP were administered intraperitoneally as single shots. In the other the same doses were injected twice on every other day.
To evaluate early changes two animals were sacrified 6, 12, and 24 hours after the administration. For damages of the highest degree and the recovery, two animals were sacrificed every other day from the second experimental day to the third week.
From electron microscopic observation in this study and mercuric induced tubular damage in the literature, administered platinum is assumed to be transferred into epithelial cells of the proximal tubules through two ways; it is partly reabsorved directly from the tubular lumen and partly from the circulating blood in the interstitial vessels through the basement membrane. The reabsorved platinum binds to SH groups of the cytoplasmic membrane and organellas resulting in impaired mitchondrial function and this mechanism is assumed to be most important in the aspect of damage process. Changes of the brush border in early stage suggest ischemia in the tissue is another affecting factor in the process.