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.
D000818:Animals; D002945:Cisplatin / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009928:Organ Specificity; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D002945:Cisplatin