EFFECT OF S-ADENOSYL-L-METHIONINE ON ETHANOL CHOLESTASIS AND HEPATOTOXICITY IN ISOLATED-PERFUSED RAT-LIVER

We investigated whether S-adenosyl-L-methionine (SAMe) influences the inhibitory effect of ethanol on bile secretion and ethanol hepatotoxic ity in the isolated perfused rat liver. SAMe (25 mg/kg intramuscularly three times a day) was administered for three days consecutively. Liv er was then isolated and perfused with taurocholate to stabilize bile secretion and exposed to 1% ethanol for 70 min. The effect of ethanol on bile flow, bile salt biliary secretion, oxygen liver consumption, A ST and LDH release in the perfusate, and hepatic concentration of glut athione, malondialdehyde, and diene conjugates was compared between SA Me-treated livers (N = 11) and paired controls (N = 11). Control exper iments without ethanol were also performed (N = 6). Exposure to 1% eth anol induced a significantly (P < 0.03) higher inhibition of bile flow (-35% vs 17%) and bile salt secretion (-28% vs 16%) in untreated comp ared with SAMe-treated livers. During 1% ethanol exposure, the release of LDH and AST in the perfusate was significantly lower (P < 0.02) in SAMe-treated livers. Oxygen liver consumption was markedly inhibited by 1% ethanol administration (P < 0.02 vs controls without ethanol), a n effect almost totally prevented by SAMe treatment (P < 0.02 vs ethan ol controls). The hepatic concentration of total glutathione was signi ficantly (P < 0.02) decreased by 1% ethanol exposure, but this effect was less pronounced in SAMe-treated than in untreated controls (P < 0. 02). The hepatic levels of malondialdehyde and diene conjugates were n ot significantly changed by ethanol exposure in either SAMe-treated or control livers in comparison to ethanol-free controls. To evaluate if SAMe protection against ethanol cholestasis was related to an effect on vesicular exocytosis, the biliary excretion of the fluid-phase mark er horseradish peroxidase was analyzed. Ethanol inhibited (P < 0.04) h orseradish peroxidase excretion, which, however, remained unaffected b y SAMe (N = 6). In conclusion, SAMe counteracted, in the IPRL, the inh ibitory effect of ethanol acute administration on bile flow and bile s alt secretion while failing to influence vesicular exocytosis. SAMe co unteracted ethanol acute hepatotoxicity.