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 the bile canalicular membrane of zone 3 hepatocytes. Thus, DCE is of value as a tool to assess the consequences of alterations in canalicular membrane integrity on bile formation. Our objective was to characterize the effects of DCE on the biliary secretion of proteins and phospholipids in freely moving rats. DCE treatment caused a rapid and sustained 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 enzymes was altered in a biphasic manner. Specifically, there was a transient fivefold increase within 30 min of DCE treatment and then a progressive decrease to approximately 10% basal levels by 4 h. Secretion of phospholipids into bile decreased rapidly in a striking and sustained manner, after DCE. Our findings of diminished lysosomal protein and phospholipid secretion following DCE treatment are consistent with an important role for canalicular membrane integrity in their entry into bile.
Woodard
S H
SH
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0609, USA.
Moslen
M T
MT
D000818:Animals; D001646:Bile / Q000378:metabolism; D001648:Bile Canaliculi / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D004000:Dichloroethylenes / Q000633:toxicity*; D004586:Electrophoresis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004000:Dichloroethylenes; D008565:Membrane Proteins; D010743:Phospholipids; D011506:Proteins; C018589:lysosomal proteins; C029297:vinylidene chloride; D007770:L-Lactate Dehydrogenase