Effects of dietary administration of 5-(3,4-dichlorophenyl)-5-ethylbarbituric acid (dichlorophenobarbital) to rats: Emphasis on hepatic drug-metabolizing enzymes and morphology

Abstract

Dietary administration of 5-(3,4-dichlorophenyl)-5-ethylbarbituric acid (0.002–0.054% drug diets) to rats for 30 days resulted in centrilobular hypertrophy of hepatocytes and dose-related increases in liver weight, hepatic microsomal protein, and the rate of p -nitroanisole O-demethylation in liver homogenates. The increase in microsomal protein was evident by electron microscopy as an increased amount of smooth endoplasmic reticulum. When rats were returned to a control diet for 2 weeks after treatment, liver weight, the concentration of microsomal protein, and the rate of p -nitroanisole metabolism were comparable to control values. Hypertrophy of the thyroid observed at the end of treatment was reversible upon withdrawal of dichlorophenobarbital. The results demonstrated that dichlorophenobarbital is a potent inducer of hepatic drug-metabolizing enzymes, and that most of the effects are rapidly reversible upon cessation of treatment.