Tauro-β-muricholate preserves choleresis and prevents taurocholate-induced cholestasis in colchicine-treated rat liver

Abstract

In recent clinical and animal experimental studies, ursodeoxycholic acid (UDCA) has been noted to have marked choleretic and cytoprotective actions. To define the mechanism and determine whether such favorable influence is specific to UDCA, the choleretic action of β-muricholic acid (β-MCA), which has a similar chemical structure, was studied using an isolated rat-liver-perfusion system. As a result, β-MCA and taurine-conjugated β-MCA (Tβ-MCA) stimulated bile flow accompanied by elevation of bile acid output and phospholipid output, and β-MCA caused an elevation in biliary HCO3− concentration in normal rat livers. After colchicine treatment, taurocholic acid (TCA) administration was associated with marked cholestasis while both β-MCA and Tβ-MCA still increased bile flow under the same conditions. Furthermore, simultaneous administration of β-MCA or, more markedly, Tβ-MCA reversed the effects of TCA alone in colchicine-treated rat liver; significant preventive effects against the cholestasis could be shown. These data suggest that β-MCA and especially Tβ-MCA can support choleresis even under conditions of colchicine-dependent microtubule dysfunction. The effects of Tβ-MCA on organelle lipids and their intracellular transport may differ from those of TCA, presumably because of the anticholestatic and cytoprotective effects of Tβ-MCA.