The effect of heavy metal chelators on the renal accumulation of platinum after cis-dichlorodiammineplatinum II administration to the rat.
1 Rats received a total of 18 mg/kg cis-dichlorodiammineplatinum (II) (CDDP) intravenously and were treated concomitantly with calcium-disodium ethylenediaminetetraacetic acid (CaNa2EDTA), 2,3-dimercaptopropanol (BAL), deferoxamine, 2,3-dimercaptosuccinic acid (DMS) or vehicle. In comparison to controls, renal platinum concentration was significantly reduced in the DMS and deferoxamine-treated groups. However, significant deterioration occurred in the deferoxamine-treated group. The hepatic platinum concentration was unaffected by the chelating agents. 2 Following a dose of 6 mg/kg CDDP intravenously, eight days of treatment with DMS, 50 mg/kg daily, had no effect on renal platinum excretion, while treatment with 100 or 200 mg/kg daily reduced renal platinum concentration by 50%. 3 In order to determine whether DMS could prevent the nephrotoxicity of CDDP, rats were given 6 mg/kg CDDP intravenously, followed by a four day course of DMS treatment at doses of 0, 50, 100 or 200 mg/kg daily begun 3 h after the CDDP dose. DMS failed to prevent renal toxicity as indicated by weight loss, serum creatinine concentration, renal histology, and the urinary excretion of N-acetyl-beta-glucosaminidase, a renal tubular enzyme.
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000378:metabolism* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010984:Platinum / Q000378:metabolism*; D051381:Rats; D004113:Succimer / Q000494:pharmacology
D002614:Chelating Agents; D010984:Platinum; D004113:Succimer; D000118:Acetylglucosaminidase; D002945:Cisplatin