ACUTE ETHANOL HEPATOTOXICITY IS MODULATED BY BILE-SALT HYDROPHILIC-HYDROPHOBIC PROPERTIES

The influence of the hydrophobic-hydrophilic properties of bile salts (BS) on acute ethanol hepatotoxicity was investigated, Bile flow, bili ary BS secretion and enzyme (LDH, AST) release in the perfusate were m easured before and after exposure to low (0.1%) or high (1%) doses of ethanol in in vitro isolated livers perfused with 1 mu M/min taurochol ate (TCA), tauroursodeoxycholate (TUDCA) or taurodeoxycholate (TDCA), Ethanol promotes a rapid decrease of basal bile flow and BS secretion in TCA-perfused livers [-28% of basal values with 0.1% (N= 6), and -35 % with 1% ethanol (N= 6)]. Bile flow and BS secretion were minimally d ecreased by ethanol in livers perfused with a hydrophilic BS (TUDCA) [ -8% decrease of basal values with 0.1% ethanol (N= 6), and -10% with 1 % ethanol (N= 9); p<0.02 vs TCA-perfused livers]. In contrast, when li vers were perfused with a hydrophobic BS (TDCA), ethanol showed a high er cholestatic effect than either TCA- or TUDCA-perfused livers. Enzym e release in the perfusate was not modified by 0.1% ethanol, while 1% ethanol promoted a 4-5 fold increase in LDH and AST release in the per fusate of TCA-perfused livers with respect to a mere 2-fold increase i n TUDCA-perfused livers and a 6-7 fold increase in TDCA perfused liver s (p< 0.03). In conclusion, we showed that TUDCA almost completely cou nteracts the cholestatic and cytolitic effects promoted by ethanol in the isolated perfused rat liver.