Protective effect of N-benzyl-D-glucamine dithiocarbamate against renal toxicity in rats during repeated cis-diamminedichloroplatinum administrations.
The protective effects of N-benzyl-D-glucamine dithiocarbamate (BGD) against the renal toxicity caused by repeated injections of cis-diamminedichloroplatinum (DDP) were studied in rats. The rats were injected i.p. with BGD (2.0 mmol/kg) immediately after i.v. injection of DDP (20 mumol/kg), and after 10 and 20 days they received repeated treatments with the same doses of DDP and BGD. Treatment with BGD prevented nephrotoxicity after repeated DDP administrations. Repeated DDP injections increased lipid peroxidation in the kidney and decreased GSH concentration in the kidney at 5 days after the third injection of DDP. BGD treatment prevented the increase in lipid peroxidation and the decrease in the GSH concentration caused by repeated administration of DDP. The determination of activities of antioxidant enzymes in the kidney showed that catalase activity decreased after repeated DDP administrations and that superoxide dismutase activity tended to decrease. Changes in activities of these enzymes were prevented by BGD treatment. The platinum concentrations in kidney and liver were decreased by BGD treatment. These results indicate that BGD treatment prevents the accumulation of platinum in the kidney after repeated administrations of DDP, resulting in protection against the DDP-induced renal toxicity.
Hidaka
S
S
Department of Pharmacy, Miyazaki Medical College Hospital, Japan.
Funakoshi
T
T
Shimada
H
H
Tsuruoka
M
M
Kojima
S
S
D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight; D002614:Chelating Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / 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; D013012:Sorbitol; D003404:Creatinine; D005978:Glutathione; C048763:N-benzylglucamine dithiocarbamate; D002945:Cisplatin