Histochemical and immunocytochemical evidence of early, selective bile canaliculi injury after 1,1-dichloroethylene in rats.
Canalicular and mitochondrial membranes were investigated as early foci of hepatocyte injury in fed and fasted male Sprague-Dawley rats given 50 mg of 1,1-dichloroethylene (DCE)/kg. Staining of the bile canaliculi localized enzymes, leucine aminopeptidase (LAP), and Mg++-dependent ATPase (Mg++-ATPase), was examined by histochemistry in frozen sections. Mitochondrial membrane enzymes, including succinate dehydrogenase, also were examined by histochemistry. Staining of two monoclonal antibodies, C-1 and 9-B1, whose binding is localized in the bile canalicular region, was examined by immunofluorescence in frozen sections. Fasted rats treated with DCE developed moderate liver damage by 4 hours as evidenced by increases in serum transaminase and bilirubin, whereas fed rats developed only slight cell damage. Centrolobular loss of immunocytochemical and histochemical canalicular staining, especially for C-1 and Mg++-ATPase, was evident as early as 1 hour after DCE and was striking by 2 hours in both fed and fasted rats. Decreases in mitochondrial enzymes were not evident histochemically in fed animals at any time after DCE and were found only at the later times in fasted animals given the toxin. Thus, DCE administration to fed rats provides a new model system of selective bile canaliculi injury.
Moslen
M T
MT
Department of Pathology, University of Texas Medical Branch, Galveston 77550.
Dunsford
H A
HA
Karnasuta
C
C
Chieco
P
P
Kanz
M F
MF
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001648:Bile Canaliculi / Q000187:drug effects / Q000201:enzymology*; D001653:Bile Ducts, Intrahepatic / Q000201:enzymology*; D001663:Bilirubin / Q000097:blood; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D004000:Dichloroethylenes / Q000633:toxicity*; D006651:Histocytochemistry; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007150:Immunohistochemistry; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D008297:Male; D009708:Nucleotidases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013385:Succinate Dehydrogenase / Q000378:metabolism
D004000:Dichloroethylenes; D006843:Hydrocarbons, Chlorinated; C029297:vinylidene chloride; D013385:Succinate Dehydrogenase; D009708:Nucleotidases; C018775:adenosine monophosphatase; D000469:Alkaline Phosphatase; D007931:Leucyl Aminopeptidase; D017301:Ca(2+) Mg(2+)-ATPase; D001663:Bilirubin