title: The effect of the administration of cobaltic protoporphyrin IX on drug metabolism, carbon tetrachloride activation and lipid peroxidation in rat liver microsomes.
abstract: The effects of cobaltic protoporphyrin IX (CPP) administration on hepatic microsomal drug metabolism, carbon tetrachloride activation and lipid peroxidation have been investigated using male Wistar rats. CPP (125 mumol/kg, 72 h before sacrifice) profoundly decreased the levels of hepatic microsomal heme, particularly cytochrome P-450. Consequently, the associated mixed-function oxidase systems were equally strongly depressed. An unexpected finding was that CPP administration also greatly decreased the activity of NADPH/cytochrome c reductase, a result not generally found with the administration of the more widely used cytochrome P-450 depleting agents, cobaltous chloride. Activation of carbon tetrachloride, measured as covalent binding of [14C] CCl4, spin-trapping of CCl3 and CCl4-stimulated lipid peroxidation, was much lower in liver microsomes from CPP-treated rats. Other microsomal lipid peroxidation systems, utilising cumene hydroperoxide or NADPH/ADP-Fe2+, were also depressed in parallel with the decrease in microsomal enzyme activities.
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000378:metabolism*; D003035:Cobalt / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000037:antagonists & inhibitors; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011166:Porphyrins / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D008054:Lipid Peroxides; D004364:Pharmaceutical Preparations; D011166:Porphyrins; D011524:Protoporphyrins; D003035:Cobalt; C007095:cobaltiprotoporphyrin; D002251:Carbon Tetrachloride; D009251:NADPH-Ferrihemoprotein Reductase; C018021:cobaltous chloride