Milkiewicz P, Mills C O, Roma M G, Ahmed-Choudhury J, Elias E, Coleman R
Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, UK.
Hepatology. 1999 Feb;29(2):471-6. doi: 10.1002/hep.510290215.
The monohydroxy bile acid, taurolithocholate (TLC), causes cholestasis in vivo and in isolated perfused livers. It is also cholestatic in vitro and, in this study using isolated rat hepatocyte couplets, causes a reduction of the accumulation of (fluorescent) bile acid in the canalicular vacuoles (cVA) of this polarized cell preparation. The hepatoprotective bile acid, tauroursodeoxycholate (TUDCA), partially protects against the action of TLC when added at the same time. It also partially reverses the cholestatic effect if added after the cells have been exposed to TLC. A second hepatoprotective compound, S-adenosyl-L-methionine (SAMe) also not only partially protects against the action of TLC when added at the same time, but it too is able to partially reverse the cholestatic effect. Neither hepatoprotective agent 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 effect in the amelioration of TLC-induced cholestasis in isolated rat hepatocyte couplets. This finding may be of possible clinical relevance.
单羟基胆汁酸牛磺石胆酸（TLC）在体内和离体灌注肝脏中均可引起胆汁淤积。它在体外也具有胆汁淤积作用，在本研究中，使用分离的大鼠肝细胞偶联物，TLC可使这种极化细胞制剂胆小管空泡（cVA）中（荧光）胆汁酸的积累减少。具有肝脏保护作用的胆汁酸牛磺熊去氧胆酸（TUDCA）在同时添加时可部分抵抗TLC的作用。如果在细胞暴露于TLC后添加，它也可部分逆转胆汁淤积作用。另一种具有肝脏保护作用的化合物S-腺苷-L-蛋氨酸（SAMe）不仅在同时添加时可部分抵抗TLC的作用，而且也能够部分逆转胆汁淤积作用。两种肝脏保护剂单独使用时均未完全有效，但它们的作用具有相加性。联合使用时，在中度胆汁淤积中可观察到cVA完全恢复，但在重度胆汁淤积中则不然。我们简要讨论了两种肝脏保护化合物相加作用模式中可能涉及的一些机制。总之，我们首次表明SAMe和TUDCA在改善分离的大鼠肝细胞偶联物中TLC诱导的胆汁淤积方面可发挥相加作用。这一发现可能具有临床相关性。
