THE EFFECT OF HEAVY METAL CHELATORS ON THE RENAL ACCUMULATION OF PLATINUM AFTER cis‐DICHLORO‐DIAMMINEPLATINUM II ADMINISTRATION TO THE RAT

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Abstract
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-climercaptopropanol (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-β-glucosaminidase, a renal tubular enzyme.