Protection against cis-diamminedichloroplatinum-induced nephrotoxicity by 2,3-dimercaptosuccinic acid in rats.
The present study was designed to examine the usefulness of 2,3-dimercaptosuccinic acid (DMSA) for the purpose of reducing cis-diamminedichloroplatinum (DDP)-induced nephrotoxicity and effective clinical use of DDP and safe. The effectiveness of DMSA on the DDP-excretion in rat kidney was observed by measuring the platinum concentration using Atomic Absorption Instrument. Co-administration of DMSA (1.0 or 2.0 mmol/kg) 1 hour after DDP injection (20 mumol/kg) showed more decrease in the platinum concentration than that immediately after DDP injection. The alleviating effect of DMSA on DDP toxicity was evaluated by lipid peroxidation, enzymatic antioxidants, and glutathione levels. The administration of DDP alone caused a significant increase in lipid peroxidation and significant decreases in enzymatic antioxidants and glutathione levels in the kidney. Co-administration of DMSA (2.0 mmol/kg) 1 hour after DDP injection showed the most effective reduction of these enzymatic damages caused by DDP. These findings suggested that the co-administration of DMSA (2.0 mmol/kg) 1 hour after DDP injection leads DDP to effective excrete from renal tissue and suppresses the lipid peroxide reaction and results in reduction of nephrotoxicity.
Mishima
K
K
Department of Pharmacy, Miyazaki Medical College Hospital, Japan.
Hidaka
S
S
Takamura
N
N
Shinozawa
S
S
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000493:pharmacokinetics / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D004113:Succimer / Q000494:pharmacology*
D000975:Antioxidants; D002614:Chelating Agents; D004113:Succimer; D005978:Glutathione; D002945:Cisplatin