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

Both an excess and an imbalance of amino acids have been associated wi th total parenteral nutrition-induced cholestasis. The present study w as 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-adenosylmethion ine at a dose of 75 mg/kg/24 h for 5 days, and compared to control rat s on dextrose alone (10.2 g/24 h) with free access to rat chow. Bile f low mu l/min) was lower (p<0.025) in the Travasol (8.65+/-0.78) than i n the control group (12.30+/-0.52) and was restored in the Travasol+S- adenosylmethionine animals (11.42+/-10). Furthermore, the bile acid se cretory 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 ex pected, the molar ratio of biliary cholesterol was lower (p<0.005) in both total parenteral nutrition groups. However, in the total parenter al nutrition group without S-adenasylmethionine, there was also a decr ease in the molar ratio of phospholipids which correlated well with th e 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<0.00 5) in the Travasol animals (6.26+/-0.53) was restored to control value s (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 memb ranes from rats on Travasol alone was abnormal, in that cholesterol an d phospholipid content as well as the lipid/protein ratio were higher than in the two other groups. However, the phospholipid species were u nchanged, These data confirm that amino acid solutions impair bile for mation and/or secretion and suggest that the provision of S-adenosylme thionine prevents this effect by maintaining normal liver plasma membr anes Na+K+-ATPase activity through preservation of the membrane lipid environment. (C) Journal of Hepatology.