Tauroursodeoxycholate and tauro-β-muricholate exert cytoprotection by reducing intrahepatocyte taurochenodeoxycholate content
Open Access
- 1 March 1993
- journal article
- research article
- Published by Wolters Kluwer Health in Hepatology
- Vol. 17 (3) , 470-476
- https://doi.org/10.1002/hep.1840170318
Abstract
Cytoprotection by tauroursodeoxycholic acid and tauro-β-muricholic acid against taurochenodeoxycholic acid-induced toxicity was examined with reference to intracellular bile acid content in primary cultured rat hepatocytes. In comparison with levels in the group administered taurochenodeoxycholic acid 1 mmol/L alone, lactate dehydrogenase levels in the culture medium decreased significantly in groups simultaneously administered taurochenodeoxycholic acid 1 mmol/L and tauroursodeoxycholic acid 0.5 to 2 mmol/L or tauro-β-muricholic acid. Results of the trypan blue uptake test indicated that the lactate dehydrogenase release was indeed caused by cell damage. After the administration of tauroursodeoxycholic acid 2 mmol/L or tauro-β-muricholic acid 2 mmol/L, intracellular taurochenodeoxycholic acid content was consistently reduced to half of that after administration of taurochenodeoxycholic acid alone. Simultaneous administration of dibutyl cyclic AMP also reduced intracellular taurochenodeoxycholic acid content and lactate dehydrogenase release. Being rinsed with tauroursodeoxycholic acid and tauro-β-muricholic acid after being precultured in taurochenodeoxycholic acid 1 mmol/L also markedly reduced their taurochenodeoxycholic acid content. Taurocholic acid caused limited reduction of intracellular taurochenodeoxycholic acid but not suppression of lactate dehydrogenase release. Taurodehydrocholic acid showed no reduction of taurochenodeoxycholic acid content and no decrease of lactate dehydrogenase release. Although only small amounts of tauroursodeoxycholic acid or tauro-β-muricholic acid were found to accumulate in hepatocytes, taurocholic acid increased as if replacing taurochenodeoxycholic acid. The results suggest that tauroursodeoxycholic acid or tauro-β-muricholic acid may exert cytoprotective effects by lowering intracellular taurochenodeoxycholic acid levels associated with their optimal hydrophilicity. (Hepatology 1993;17:470-476.)Keywords
This publication has 16 references indexed in Scilit:
- Tauro-β-muricholate preserves choleresis and prevents taurocholate-induced cholestasis in colchicine-treated rat liverGastroenterology, 1992
- A study of the mechanism of cytoprotective bile acid with reference to intracellular bile acid analysis.Kanzo, 1992
- Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile saltsGastroenterology, 1991
- Acute effects of ursodeoxycholic and chenodeoxycholic acid on the small intestinal absorption of bile acidsGastroenterology, 1990
- Tauro β-muricholate is as effective as tauroursodeoxycholate in preventing taurochenodeoxycholate-induced liver damage in the ratLife Sciences, 1990
- Mechanisms of Bile Secretion: lnsights from the Isolated Rat Hepatocyte CoupletSeminars in Liver Disease, 1988
- IS URSODEOXYCHOLIC ACID AN EFFECTIVE TREATMENT FOR PRIMARY BILIARY CIRRHOSIS?The Lancet, 1987
- Anti-cholestatic and cytoprotective properties of ursodeoxycholic acid. Studies in vivo and vitro.Kanzo, 1987
- Effect of taurochenodeoxycholate or tauroursodeoxycholate upon biliary output of phospholipids and plasma-membrane enzymes, and the extent of cell damage, in isolated perfused rat liversBiochemical Journal, 1983
- Tauroursodeoxycholate prevents taurocholate induced cholestasisLife Sciences, 1982