Alterations in rat liver microsomal and lysosomal β-glucuronidase by compounds which induce hepatic drug-metabolizing enzymes

Abstract

Chlordane, dieldrin, piperonyl butoxide, and benzpyrene, which induce the hepatic microsomal mixed function oxidases and UDP glucuronyltransferases, decreased activity of smooth and rough endoplasmic reticulum β-glucuronidase. The reduction occurred when either p-nitrophenyl β- D-glucuronide or phenolphthalein mono-β-glucuronide was used as the substrate. Chlordane or dieldrin pretreatment of rats for 3 days resulted in a 2.5-fold reduction in endoplasmic reticulum activity while the reduction was less for piperonyl butoxide or benzpyrene. On the other hand, aminopyrine demethylase and UDP glucuronyltransferase were increased 2-fold by chlordane or dieldrin pretreatments. Decreases in microsomal β-glucuronidase activity might be directly or indirectly involved in the induction process since decreases in β-glucuronidase activity are quantitatively similar to increases in activity of the drug-metabolizing enzymes. Lysosomal β-glucuronidase also decreased following pretreatment of rats with inducing agents, but the reduction was less than that observed in the endoplasmic reticulum fractions. Analysis of pH optima, temperature optima, K m values, heat denaturation data, and effects of Triton X-100 on activities of various liver fractions suggests that β-glucuronidase from the endoplasmic reticulum and lysosomes have similar properties.