Bile acid transport and metabolism in rat liver slices. 2006

Astrid Barth, and Jerome Braun, and Dieter Müller
Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, 07740 Jena, Germany. Astrid.Barth@mti.uni-jena.de

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.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D002635 Chenodeoxycholic Acid A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. Chenic Acid,Chenodeoxycholate,Chenodiol,Gallodesoxycholic Acid,Chenique Acid,Chenix,Chenofalk,Chenophalk,Henohol,Quenobilan,Quenocol,Sodium Chenodeoxycholate,Acid, Chenic,Acid, Chenique,Acid, Chenodeoxycholic,Acid, Gallodesoxycholic,Chenodeoxycholate, Sodium
D002756 Cholagogues and Choleretics Gastrointestinal agents that stimulate the flow of bile into the duodenum (cholagogues) or stimulate the production of bile by the liver (choleretic). Choleretics,Cholagogues,Cholagogues, Choleretics,Choleretics and Cholagogues,Hydrocholeretics
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic
D013655 Taurochenodeoxycholic Acid A bile salt formed in the liver by conjugation of chenodeoxycholate with taurine, usually as the sodium salt. It acts as detergent to solubilize fats in the small intestine and is itself absorbed. It is used as a cholagogue and choleretic. Chenodeoxycholyltaurine,Taurine Chenodeoxycholate,Taurochenodeoxycholate,Acid, Taurochenodeoxycholic,Chenodeoxycholate, Taurine

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