Alterations in hepatic and renal levels of glutathione and activities of glutathione S-transferase from rats treated with cis-dichlorodiammineplatinum-II.

Adult female rats were treated intraperitoneally with 8 mg/kg of cis-dichlorodiammineplatinum(II). At various times after treatment 1, 3, 5, 8, 12 days replicate animals were killed and liver and kidney cytosols examined for activity of glutathione-dependent transferase activities and levels of glutathione. Hepatic levels of glutathione were depressed by 13-28% at 1, 3, 5 days after dosing. Renal levels of glutathione were increased by 3-5 fold at 8 and 12 days after drug administration. Renal levels of glutathione were decreased at nearly all times studied with a nadir at 5 days. Activity of glutathione s-acryl transferase was increased and S-epoxidetransferase was decreased at 5, 8, 12 days after dosing. When cisplatinum was added to incubation mixtures in vitro, no changes in enzyme activities were observed. When cisplatin and reduced glutathione were determined chromatographically in tissue cytosols from treated rats, 30% of the recovered platinum was associated with glutathione. In tissue cytosols, greater than 95% of the total platinum content was retained in the supernatant when protein was precipitated with trichloroacetic acid, while only 3-5% of the protein was retained.