The induction of rat hepatic microsomal xenobiotic metabolism by n-octadecyl β-(3′,5′-di- tert-butyl-4′-hydroxyphenyl)-propionate

Abstract

The hepatic effects of oral administration of n-octadecyl β-(3′,5′-di- tert-butyl-4′-hydroxyphenyl)propionate (OBPP) has been studied in male and female rats. OBPP administration produced both marked liver enlargement and the induction of a number of parameters of hepatic microsomal xenobiotic metabolism, including cytochrome P-450, mixed-function oxidase enzymes and UDPglucuronosyltransferase. Histological examination of liver sections from OBPP-treated rats revealed hypertrophy of the centrilobular cells of the liver lobule, and ultrastructural studies indicated a marked proliferation of the smooth endoplasmic reticulum. Reversibility studies demonstrated that the increase in liver size and in the activities of xenobiotic-metabolizing enzymes had substantially reverted to control levels 14 days after the cessation of OBPP treatment. It is concluded that OBPP is a potent inducer of hepatic xenobiotic metabolism in the rat, with properties similar to those of sodium phenobarbitone.