Rapid Stimulation of Free Glucuronate Formation by Non-glucuronidable Xenobiotics in Isolated Rat Hepatocytes*

Vitamin C synthesis in rat liver is enhanced by several xenobiotics, including aminopyrine and chloretone. The effect of these agents has been linked to induction of enzymes potentially involved in the formation of glucu-ronate, a precursor of vitamin C. Using isolated rat hepatocytes as a model, we show that a series of agents (aminopyrine, antipyrine, chloretone, clotrimazole, me-tyrapone, proadifen, and barbital) induced in a few min-utes an up to 15-fold increase in the formation of glucu-ronate, which was best observed in the presence of sorbinil, an inhibitor of glucuronate reductase. They also caused an 2-fold decrease in the concentration of UDP-glucuronate but little if any change in the concen-tration of UDP-glucose. Depletion of UDP-glucuronate with resorcinol or D-galactosamine markedly decrease