Toxicity of cis-diamminedichloroplatinum (II) (cisplatin) in the frog, Rana pipiens.

The toxicity of the anti-cancer drug cis-diamminedichloroplatinum (II) (cisplatin), at 2 to 40 mg per kg, was studied in the frog, Rana pipiens. The LD50 for the drug was approximately 17 mg per kg. Major non-nervous system toxicity occurred in the kidney. Renal failure was manifested as anasarca and increasing blood urea nitrogen (BUN). Histopathological changes included acute tubular necrosis and tubular dilatation, which were more severe at higher doses. Interstitial fibrosis occurred after prolonged survival after a single dose. Ultrastructurally, there was increased electron-dense material in tubular cells, but no specific changes in mitochondria or nuclear structures were seen. Gastro-intestinal toxicity was less severe than in other species and was more prominent at higher doses. Pathological changes consisted of epithelial nuclear atypia and apoptosis. By electron microscopy, there was increased separation of cell borders, depletion of chylomicrons and mucin granules and increases in electron-dense material. Again no specific mitochondrial or nuclear changes were seen. Relatively slight changes were seen in the liver, consisting of altered distribution of rough endoplasmic reticulum and dispersion of nuclear chromatin. Minimal pathology was demonstrated in the haematopoietic system or in the gonads. Thus toxicity of cisplatin in the frog is similar to that seen in mammals, including rodents and man.