Stimulation of microsomal drug oxidation in liver and kidney of rats treated with the oncolytic agent cis-dichlorodiammineplatinum-II

In vitro drug metabolism from liver and kidney of rats was studied for up to 12 days following a single intraperitoneal injection of the antineoplastic drug cisplatinum. At 3, 5, and 8 days posttreatment, hepatic cytochrome P-450 dependent enzyme activity was increased 20–45%, but levels of cytochromes P-450 and b₅ were unaltered. Hepatic in vitro stimulated thiobarbituric acid reactive (TBAR) substances were increased at all times, with a maximum of 20 times normal on day 5. Renal aniline hydroxylase activity was elevated 25–95% throughout the first 8 days. Renal in vitro stimulated TBAR substances were not significantly altered. In vitro addition of cisPt to control microsomes resulted in no consistent, dose-related changes in substrate metabolism.