Tauroursodeoxycholate and S-adenosyl-L-methionine exert an additive ameliorating effect on taurolithocholate-induced cholestasis: A study in isolatedrat hepatocyte couplets

The monohydroxy bile acid, taurolithocholate (TLC), causes cholestasis in v ivo and in isolated perfused livers. It is also cholestatic in vitro and, i n this study using isolated rat hepatocyte couplets, causes a reduction of the accumulation of (fluorescent) bile acid in the canalicular vacuoles (cV A) of this polarized cell preparation. The hepatoprotective bile acid, taur oursodeoxycholate (TUDCA), partially protects against the action of TLC whe n added at the same time. It also partially reverses the cholestatic effect if added alter the cells have been exposed to TLC, A second hepatoprotecti ve compound, S-adenosyl-L-methionine (SAMe) also not only partially protect s against the action of TLC when added at the same time, but it too is able to partially reverse the cholestatic effect. Neither hepatoprotective agen t is fully effective alone, but their effects are additive. In combination, a full restoration of cVA is observed in moderate cholestasis, but not in severe cholestasis, We discuss briefly some possible mechanisms involved in the additive mode of action of both hepatoprotective compounds, In summary , we show for the first time that SAMe and TUDCA can exert an additive effe ct in the amelioration of TLC-induced cholestasis in isolated rat hepatocyt e couplets, This finding may be of possible clinical relevance.