Protective Effects of Dithiocarbamates against Renal Toxicity of cis-Diamminedichloroplatinum in Rats

Sodium diethyldithiocarbamate (DDTC), sodium N-benzyl-o-glucamine dithiocarbamate(BGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), and sodium N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD) were evaluated for efficacy as inhibitors of cisdiamminedichloroplutinum (DDP)-induced nephrotoxicity in a rat model. Treatments with 2.0 mmollkg of BGD, HBGD, and CBGD immediately after DDP (20 µmollkg) injection effectively prevented the nephrotoxic effects of DDP, but administration of DDTC immediately after DDP injection afforded a small protection. Concurrent treatment with 0.5 or 1.0 mmollkg of HBGD, or 1.0 mmollkg of CBGD could prevent DDP-induced renal damage. A significant decrease in weight loss was also observed in these dithiocarbamaterescued rats. The platinum concentrations in liver and kidney were significantly decreased by BGD, HBGD, and CBGD treatments, respectively. The antitumor efficacy of DDP in the Walker 256 carcinoma-bearing rats was not affected by administration of...