Protective effects of dithiocarbamates against renal toxicity of cis-diamminedichloroplatinum in rats.
Sodium diethyldithiocarbamate (DDTC), sodium N-benzyl-D-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 cis-diamminedichloroplatinum (DDP)-induced nephrotoxicity in a rat model. Treatments with 2.0 mmol/kg of BGD, HBGD, and CBGD immediately after DDP (20 mumol/kg) 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 mmol/kg of HBGD, or 1.0 mmol/kg of CBGD could prevent DDP-induced renal damage. A significant decrease in weight loss was also observed in these dithiocarbamate-rescued 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 HBGD (1.0 mmol/kg) or CBGD (1.0 mmol/kg). The results of this study indicated that the injection of HBGD or CBGD to rats treated with DDP can protect against DDP-induced nephrotoxicity more effectively than DDTC or BGD.
Hidaka
S
S
Department of Pharmacy, Miyazaki Medical College Hospital, Japan.
Tsuruoka
M
M
Funakoshi
T
T
Shimada
H
H
Kiyozumi
M
M
Kojima
S
S
D000818:Animals; D002279:Carcinoma 256, Walker / Q000188:drug therapy; D002614:Chelating Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000009:adverse effects* / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D004050:Ditiocarb / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013012:Sorbitol / Q000031:analogs & derivatives / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology
D002614:Chelating Agents; D013859:Thiocarbamates; C068198:N-4-hydroxymethylbenzylglucamine dithiocarbamate; C068199:N-4-carboxybenzylglucamine dithiocarbamate; D013012:Sorbitol; D004050:Ditiocarb; C048763:N-benzylglucamine dithiocarbamate; D002945:Cisplatin