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THE EFFECT OF HEAVY METAL CHELATORS ON THE RENAL ACCUMULATION OF PLATINUM AFTER cis‐DICHLORO‐DIAMMINEPLATINUM II ADMINISTRATION TO THE RAT
Author(s) -
GRAZIANO JOSEPH,
JONES BRIAN,
PISCIOTTO PATRICIA
Publication year - 1981
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1981.tb16800.x
Subject(s) - deferoxamine , ethylenediaminetetraacetic acid , nephrotoxicity , chemistry , creatinine , toxicity , pharmacology , kidney , excretion , chelation , medicine , biochemistry , inorganic chemistry , organic chemistry
1 Rats received a total of 18 mg/kg cis ‐dichlorodiammineplatinum (II) (CDDP) intravenously and were treated concomitantly with calcium ‐disodium ethylenediaminetetraacetic acid (CaNa 2 EDTA), 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.