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Tauroursodeoxycholate and S‐adenosyl‐L‐methionine exert an additive ameliorating effect on taurolithocholate‐induced cholestasis: A study in isolated rat hepatocyte couplets
Author(s) -
Milkiewicz Piotr,
Mills Charles O.,
Roma Marcelo G.,
AhmedChoudhury Jalal,
Elias Elwyn,
Coleman Roger
Publication year - 1999
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510290215
Subject(s) - cholestasis , hepatocyte , in vivo , vacuole , methionine , bile acid , pharmacology , in vitro , chemistry , biochemistry , biology , endocrinology , cytoplasm , amino acid , microbiology and biotechnology
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