1989 Volume 80 Issue 4 Pages 517-525
Nephrotoxic effects of cis-Diammine-1, 1-cyclobutane dicarboxylate platinum II (CBDCA) were investigated in male 6 weeks old Wistar rats. The animals were divided into 4 groups: Group I (each received a single intraperitoneal injection of CBDCA 80, 120mg/kg); Group II (a single intraperitoneal injection of CBDCA 80, 120mg/kg after withdrawal of food and water for 2 days); Group III (intravenous administration of CBDCA 15, 30mg/kg for 7 consecutive days after withdrawal of food and water for 2 days); Group IV (controls).
Rats from each group were sacrificed at 3, 7, 10 and 14 days following the start of the experiment. Serum levels of BUN and creatinine were then measured and renal histopathological examination was conducted by light and electron microscopy. In addition, the total platinum concentration in the serum was measured in Group I, and X-ray microanalysis was performed after intraperitoneal administration of CBDCA (100mg/kg) and cis-Diamminedichloroplatinum (II) (CDDP) (6mg/kg) for 2 consecutive days (Group V).
The results showed increased levels of BUN in each group due to catabolism. No significant increase in serum creatinine was observed and there appeared to be no evidence of renal dysfunction. For all groups, localized vacuolar degeneration in the epithelial cells of the tubules was predominantly apparent. Electron microscopy revealed only degeneration of the epithelium mainly in the proximal tubules and also showed reabsorption of platinum from the lumen of the tubules. X-ray microanalysis on the rat kidney receiving CDDP revealed the presence of platinum ions in the epithelial cells of the tubules, but it was not detected after higher doses of CBDCA. The difference in the affinity for serum proteins between the two platinum compounds suggests that CBDCA is excreted into the urine by glomerular filtration and CDDP mainly by secretion into the tubules. Therefore, the difference of urine excretory mechanisms between the two platinum compounds seems to be most related with nephrotoxicity.