REVERSIBLE BILE-ACID CHANGES IN BILE-DUCT OBSTRUCTION AND ITS POTENTIAL FOR HEPATOCELLULAR INJURY

The etiology of hepatocellular dysfunction resulting from chronic biliary obstruction is not clearly understood. Alterations in bile acid metabolism due to changes in microsomal cytochrome P-450 enzyme activities may have a fundamental role in cholestatic liver injury. This study examines the very early changes in both biliary bile acids and hepatic microsomal cytochrome P-450 content after bile duct obstruction in the rat and the effects of the restoration of bile flow after 3 days of biliary obstruction. We found that early induction of cytochrome P-450 may be a fundamental step in the generation of cholestatic liver injury mediated by hepatotoxic bile acids. The rapid reversal of bile acid changes with reconstituted bile flow indicate that the liver is able to quickly recover when obstruction is relieved. Characterization of this fundamental process may ultimately provide a means of modulation of cholestatic hepatotoxicity.