Bile acid transport and metabolism in rat liver slices.
To further characterise precision-cut liver slices from 34- to 40-day-old male rats as an in vitro model for bile acid (BA) metabolism and transport, the effect of the primary BAs cholic (CA, 5 microM) and chenodeoxycholic acid (CDCA, 0.15 and 0.75 microM) as well as of the therapeutically used tauroursodeoxycholic acid (T-UDCA, 5 microM) on BA profiles was investigated. After 4 h incubation in 5 ml Krebs-Henseleit buffer (KHB) 26 individual BAs were determined in slices (50 mg liver/5 ml KHB) and medium by HPLC with postcolumn derivatisation and fluorescence detection. In control incubations, mean total BA concentrations were 5.09 nmol/50 mg liver (101.80 nmol/g liver) in slices and 25.71 nmol/5 ml KHB, among them 72% taurine-(T-), 22% glycine-(G-) conjugated and 6% free BAs in tissue and medium. The main BAs were beta-muricholic (beta-MCA and conjugates) and cholic acids (CA and conjugates) in tissue and medium. The following results were obtained after addition of CDCA, CA, and T-UDCA, respectively, to the KHB. The toxic CDCA was quantitatively converted mainly to T-UDCA and taurohyodeoxycholic (T-HDCA) acid. CA was conjugated in equal shares to T- and G-CA, whereas T-UDCA was enriched in slices and hydroxylated half to T-beta-MCA, which is the main BA in rats. In conclusion, rat liver slices are highly effective not only in uptake, conjugation and excretion of BAs but also in conversion of strong detergent into less toxic BAs.
Barth
Astrid
A
Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, 07740 Jena, Germany. Astrid.Barth@mti.uni-jena.de
Braun
Jerome
J
Müller
Dieter
D
D000818:Animals; D001692:Biological Transport; D002635:Chenodeoxycholic Acid / Q000378:metabolism; D002756:Cholagogues and Choleretics / Q000378:metabolism*; D019826:Cholic Acid / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D013655:Taurochenodeoxycholic Acid / Q000378:metabolism*
D002756:Cholagogues and Choleretics; D002635:Chenodeoxycholic Acid; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D019826:Cholic Acid