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Gadeholt G: Ethanol-inducible cytochrome P-450 is more susceptible to in vitro carbon tetrachloride-mediated destruction than phenobarbital-inducible and beta-naphthoflavone-inducible cytochromes P-450. Acta Pharmacol Toxicol. 1984 Sep;55(3):216-23.
Liver microsomes were incubated aerobically in vitro with NADPH and carbon tetrachloride in the presence of 1.5 mM EDTA. The resulting losses of haemoproteins and monooxygenase activities were evaluated after washing. Microsomes from ethanol-pretreated rats lost about 66% of their cytochrome P-450 measured as such, together with 94% of their ethoxycoumarin 0-deethylase activity. Microsomes from control and phenobarbital-pretreated rats lost between 30 and 35% of their cytochrome P-450 and between 65 and 50% of the ethoxycoumarin 0-deethylase activity. Microsomes from beta-naphtoflavone-pretreated rats lost about 10% of their cytochrome P-450 and 13% of their ethoxycoumarin 0-deethylase activity. The inhibition with tetrahydrofuran, metyrapone and alpha-naphtoflavone were also changed after incubation, suggesting selective destruction of isoenzymes with high affinity for tetrahydrofuran and selective sparing of others. Studies of 4-nitroanisole 0-demethylation indicated selective destruction of enzymes with high affinity for the 4-nitroanisole and sparing of enzymes with lower affinity. The properties that were destroyed after incubation with carbon tetrachloride were those that were elevated after chronic ethanol feeding. The destructive action of carbon tetrachloride in microsomes from ethanol-pretreated rats was found to be different from those of allyl alcohol and 2-isopropyl 4-pentenamide. The findings may have relevance to the enhancement of chronic ethanol feeding on the hepatotoxicty of carbon tetrachloride. |
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