675 Effects of Monohydroxy Bile Acids on Bile Acid Transport in Newborn Rabbit Hepatccytes

Abstract

Neonatal obstructive jaundice, neonatal hepatitis, and congenital biliary atresia are thought to be caused by the toxic effects of bile acids, especially toxic monohydroxy bile acids. These studies were performed to examine the effects of lithocolic acid (LCA) and taurolithocholic acid (TLCA) on cellular toxicity, bile acid uptake and secretion in freshly isolated hepatccytes from newborn and 23 day old rabbits. Cellular bile acid uptake and secretion were quantitated using radiolabelled glycocholic acid. Both control and treated hepatocytes were incubated for one hour in the presence of varying concentrations of monohydroxy bile acids prior to kinetic analysis of bile acid transport. A summary of transport data for hepatocytes from 23 day old rabbits is presented in the table. Hepatocytes from 4 day old rabbit under control conditions showed only negligible secretion of bile acid. The effects of LCA and TLCA on bile acid uptake in hepatocytes from 4 day old rabbits were similar to those observed with hepatccytes from 23 day old rabbit. Electron microscopy revealed that the most striking effects of monohydroxy bile acids were on the bile canaliculi (BC). The EC were greatly dilated with prominent thickening and fewer and irregular microvilli. It is concluded that BC function is selectively sensitive to disruption by monohydroxy bile acids and demonstrates significant post natal maturation.