Biliary excretion of marker solutes by rats with 1,1-dichloroethylene-induced bile canalicular injury.
Our objective was to characterize the effects of 1,1-dichloroethylene (DCE, 50 mg/kg) on bile formation by freely moving rats. This toxicant provides a new tool to study structure-function associations because it selectively injures zone 3 bile canaliculi of fed rats. Ultrastructural changes included loss of microvilli from the canalicular membrane and membrane fragments within the dilated canalicular lumens. Function studies compared biliary excretion of a battery of endogenous and exogenous marker solutes during a basal period versus that at 1 and 3 hr after toxicant treatment. DCE treatment had the following effects on biliary functions in fed rats: a slowing of organic anion transport into bile; a decrease in biliary total protein content; a striking increase in biliary leucine aminopeptidase, a canalicular membrane protein; and an accentuation of the early entry of horseradish peroxidase into bile without a change in the total amount of this large protein recovered in bile. In contrast, bile flow and bile salt excretion were not altered, Pi continued to be excluded from bile, and D-glucose continued to be reabsorbed from bile. The observed alterations in biliary functions and canalicular structure may ensue from the metabolism of DCE to semistable glutathione conjugates that congregate near the canaliculi en route to biliary excretion.
Department of Pathology, University of Texas Medical Branch, Galveston 77555-0605.
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Kanz
D000818:Animals; D000838:Anions / Q000378:metabolism; D001646:Bile / Q000187:drug effects* / Q000378:metabolism; D001648:Bile Canaliculi / Q000187:drug effects* / Q000648:ultrastructure; D004000:Dichloroethylenes / Q000378:metabolism / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008854:Microscopy, Electron; D008871:Microvilli / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D000838:Anions; D004000:Dichloroethylenes; D008565:Membrane Proteins; C029297:vinylidene chloride; D006735:Horseradish Peroxidase; D007931:Leucyl Aminopeptidase; D005947:Glucose