Effect of partial hepatectomy on the responsiveness of microsomal enzymes and cytochrome P-450 to phenobarbital or 3-methylcholanthrene

Abstract

The effects of phenobarbital and 3-methylcholanthrene (3-MC) pretreatment on liver weight, microsomal protein, cytochrome P-450 content, microsomal aniline hydroxylase, hexobarbital hydroxylase and P-nitroanisole O-demethylase activities have been studied in control, sham-operated and partially hepatectomized rats. In unoperated rats, phenobarbital pretreatment significantly increased liver weight, microsomal protein, P-450 content and enzyme activities toward all three substrates. 3-MC pretreatment significantly increased liver weight, P-450 content and p-nitroanisole O-demethylation without influencing the other parameters. When administered to shamoperated or partially hepatectomized rats, phenobarbital and 3-MC caused substantially the same effects, though the magnitude of the effects was less than in unoperated animals. Thus, significant increases were seen in the various parameters after injection of phenobarbital or 3-MC into hepatectomized rats. It is concluded that the regenerating liver, like the fetal or newborn liver and certain rodent hepatomas, although exhibiting low levels of microsomal enzymes, has the capacity to respond to the enzyme inducers, phenobarbital and 3-MC. Differential comparison of the enzyme changes expressed in terms of microsomal protein and also in terms of microsomal P-450 content revealed that the activity of the enzymes catalyzing p-nitroanisole and aniline oxidations parallel the microsomal P-450 content more closely than does the enzyme catalyzing hexobarbital hydroxylation.