Elevation of individual serum bile acids on exposure to trichloroethylene or alpha-naphthylisothiocyanate.
Rats were treated with trichloroethylene via intraperitoneal (ip) injection or inhalation, or with ip alpha-naphthylisothiocyanate (ANIT). Serum samples were assayed for indices of liver injury including alanine aminotransferase (ALT), sorbitol dehydrogenase (SDH), alkaline phosphatase (AP), and bilirubin. Liver from some rats was examined for histological appearance. These data were compared to levels of individual serum bile acids (SBA) determined by high-performance liquid chromatography. Trichloroethylene and ANIT, each at their highest dose only, caused elevations in ALT, but not SDH or AP. The highest dose of ANIT also caused elevated serum bilirubin and cholangitis in the liver. SBA were also elevated in response to both trichloroethylene and ANIT, but at doses below those at which other parameters of liver function were increased. For both chemicals, taurocholic acid was the most sensitive of the bile acids assayed, being elevated at the lowest doses tested of 10 mumols/kg for trichloroethylene and 5 mumols/kg for ANIT. As the doses were raised more of the individual bile acids showed increases. On exposure to trichloroethylene via inhalation taurocholic acid was one of two SBA to show elevation. Thus, both trichloroethylene and ANIT cause elevation in SBA at doses well below those which cause an increase in standard indicators of liver dysfunction. This suggests that SBA and perhaps taurocholic acid, in particular, may provide a sensitive tool for studying hepatobiliary effects of chemicals.
Wang
G F
GF
National Institute of Occupational Health and Safety, University of Sydney, NSW, Australia.
Stacey
N H
NH
D015058:1-Naphthylisothiocyanate / Q000633:toxicity*; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood*; D001663:Bilirubin / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014241:Trichloroethylene / Q000633:toxicity*
D001647:Bile Acids and Salts; D014241:Trichloroethylene; D015058:1-Naphthylisothiocyanate; D007064:L-Iditol 2-Dehydrogenase; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin