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The effect of the administration of cobaltic protoporphyrin IX on drug metabolism, carbon tetrachloride activation and lipid peroxidation in rat liver microsomes

Chemico-Biological Interactions, ISSN: 0009-2797, Vol: 50, Issue: 2, Page: 143-151
1984
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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 μmol/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 [ 14 C] CCl 4, spin-trapping of CCl 3 and CCl 4 -stimulated lipid peroxidation, was much lower in liver microsomes from CPP-treated rats. Other microsomal lipid peroxidation systems, utilising cumene hydroperoxide or NADPH/ADP-Fe 2+, were also depressed in parellel with the decrease in microsomal enzyme activities.

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