DECREASED BILIARY-SECRETION OF PROTEINS AND PHOSPHOLIPIDS BY RATS WITH 1,1-DICHLOROETHYLENE-INDUCED BILE CANALICULAR INJURY

1,1-Dichloroethylene (DCE, 50 mg/kg) rapidly and selectively injures t he bile canalicular membrane of zone 3 hepatocytes. Thus, DCE is of va lue as a tool to assess the consequences of alterations in canalicular membrane integrity on bile formation. Our objective was to characteri ze the effects of DCE on the biliary secretion of proteins and phospho lipids in freely moving rats. DCE treatment caused a rapid and sustain ed decrease in total biliary protein output. In contrast, canalicular membrane-localized enzyme activities more slowly increased to 8- to 15 -fold in bile from DCE-treated rats, Biliary output of lysosomal enzym es was altered in a biphasic manner. Specifically, there was a transie nt fivefold increase within 30 min of DCE treatment and then a progres sive decrease to approximately 10% basal levels by 4 h, Secretion of p hospholipids into bile decreased rapidly in a striking and sustained m anner after DCE. Our findings of diminished lysosomal protein and phos pholipid secretion following DCE treatment are consistent with an impo rtant role for canalicular membrane integrity in their entry into bile . (C) 1998 Academic Press.