S-ADENOSYLMETHIONINE PREVENTS TOTAL PARENTERAL NUTRITION-INDUCED CHOLESTASIS IN THE RAT

Both an excess and an imbalance of amino acids have been associated with total parenteral nutrition-induced cholestasis. The present study was undertaken to further our understanding of this condition in light of observations that methyl donor amino. acids may be protective. Rats were maintained on Travasol(R) (3.4 g amino acids/24 h) and dextrose (10.2 g/24 h) with and without the ''active methyl'' S-adenosylmethionine at a dose of 75 mg/kg/24 h for 5 days, and compared to control rats on dextrose alone (10.2 g/24 h) with free access to rat chow. Bile flow mu l/min) was lower (p<0.025) in the Travasol (8.65+/-0.78) than in the control group (12.30+/-0.52) and was restored in the Travasol+S-adenosylmethionine animals (11.42+/-10). Furthermore, the bile acid secretory rate (mu mol/h) was higher p<0.05) with S-adenosylmethionine (23.34+/-3.71). than without S-adenosylmethionine (14.16+/-2.19). As expected, the molar ratio of biliary cholesterol was lower (p<0.005) in both total parenteral nutrition groups. However, in the total parenteral nutrition group without S-adenasylmethionine, there was also a decrease in the molar ratio of phospholipids which correlated well with the bile acid secretory rate. Analysis of liver plasma membranes showed that a lower activity of Na+K+-ATPase (mu mol Pi/mg protein/h) (p<0.005) in the Travasol animals (6.26+/-0.53) was restored to control values (15.20+/-1.43) by the addition of S-adenosylmethionine (17.07+/-2.87), In the three groups, a close correlation was observed between Na+K+-ATPase activity and bile flow. Lipid composition of liver plasma membranes from rats on Travasol alone was abnormal, in that cholesterol and phospholipid content as well as the lipid/protein ratio were higher than in the two other groups. However, the phospholipid species were unchanged, These data confirm that amino acid solutions impair bile formation and/or secretion and suggest that the provision of S-adenosylmethionine prevents this effect by maintaining normal liver plasma membranes Na+K+-ATPase activity through preservation of the membrane lipid environment. (C) Journal of Hepatology.