CIS-DIAMMINEDICHLOROPLATINUM(II) NEPHROTOXICITY AND ITS RELATIONSHIP TO RENAL GAMMA-GLUTAMYL-TRANSFERASE TRANSPEPTIDASE AND GLUTATHIONE

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (12) , 6072-6076
Abstract
To investigate the mechanism of cis-diamminedichloroplatinum(II) (cisplatin) nephrotoxicity, male Spargue-Dawley rats were given 1 injection of cisplatin (6 mg/kg i.v.). Urinary levels of amino acids and .gamma.-glutamyl transpeptidase were monitored for 8 days; kidney homogenate content of .gamma.-glutamyl transpeptidase was followed for 50 h and that of S-dependent glutathione peroxidase and total glutathione was followed for 4 h. Peak urinary levels of amino acids and .gamma.-glutamyl transpeptidase occurred 4.5 h after the i.v. dose. Glutamine, glycine and ethanolamine were all elevated > 20 times that of the control at 4.5 h and were still significantly elevated at 50 h. Total renal glutathione content increased 51 .+-. 17% (SD) of control values 20 min after cisplatin was given, before returning to base-line levels. No depletion of renal glutathione or glutathione peroxidase was detected over the time interval studied. These results demonstrate an earlier physiological impairment than has hitherto been shown. Depletion of glutathione and glutathione peroxidase does not occur in the rat kidney following therapeutic doses of cisplatin.