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Mid-Western Regional Society of Toxicology: Novel Mechanisms of Hepatobiliary Toxicity

This minisymposium focused on novel research in hepatotoxicity relative to the hepatobiliary system. Three extended abstracts from this meeting are published to provide an overview of the major points covered at the meeting. Dr. Mary Vore of the University of Kentucky reviewed the work that her laboratory has undertaken to understand the mechanisms of steroid glucuronide-induced cholestasis. Dr. Vore’s laboratory has pursued the finding that the glucuronide conjugates of the steroid Dring are cholestatic in the rat and decrease bile secretory function in the rhesus monkey. Using the D-ring glucuronide, estradiol-17beta-(beta-D-glucuronide) (E2-17G), and MDR-positive cells (which express P-glycoprotein at very high levels), her lab has shown recently that interaction of P-glycoprotein with E2-17G plays a significant role in inducing cholestasis in this model. Dr. Hartmut Jaeschke of The Upjohn Company discussed his work involving glutathione (GSH)-dependent defense mechanisms against intracellular and vascular oxidant stress in the liver. Dr. Jaeschke outlined the im-