Prevention of renal toxicity of cis-diamminedichloroplatinum by dithiocarbamates in rats.
The protective effects of various dithiocarbamates such as N-benzyl-D-glucamine dithiocarbamate (BGD), N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD), and N-methyl-D-glucamine dithiocarbamate (MGD) on DDP-induced renal toxicity in rats were studied. The rats received the simultaneous i.v. injection of DDP (20 mumol/kg) and a chelating agent (40 mumol/kg). Significant increase in blood urea nitrogen (BUN) level was observed 5 days after DDP injection. The increase in BUN level was completely prevented by only HBGD and CBGD among these chelating agents. Treatment with CBGD completely prevented against DDP-induced body weight loss. BGD and MGD treatment did not prevent the increase in BUN level or body weight loss. HBGD and CBGD were the most effective in decreasing the renal platinum content, resulting in maximum protection against the DDP-induced renal damage. The antitumor efficacy of DDP in the Walker 256 carcinoma-bearing rats was not affected by CBGD administration.
Shimada
H
H
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Sugimachi
N
N
Funakoshi
T
T
Kojima
S
S
D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013012:Sorbitol / Q000031:analogs & derivatives / Q000494:pharmacology; D013113:Spin Labels; D013859:Thiocarbamates / Q000494:pharmacology*
D002614:Chelating Agents; D013113:Spin Labels; D013859:Thiocarbamates; C068198:N-4-hydroxymethylbenzylglucamine dithiocarbamate; C068199:N-4-carboxybenzylglucamine dithiocarbamate; D013012:Sorbitol; C041262:N-methyl-D-glucamine dithiocarbamate; C048763:N-benzylglucamine dithiocarbamate; D002945:Cisplatin