78 S-ADENOSYLMETHIONINE (SAMe) REVERSES TOTAL PARENTERAL NUTRITION(TPN)-ASSOCIATED CHOLESTASIS

Abstract

The quantity of perfused amino acids (aa), and their qualitative pattern, was thought to be a pathogenic factor of TPN-associated hepatotoxicity. Previous studies have shown an hypothetic protective effect of methyl donor aa. To assess whether and how SAMe could normalize bile flow during infusion of aa with dextrose, 4 groups of rats (157-180g) were studied after 5 days of TPN (Vamin(V) or Travasol(T) with and without SAMe), as well as a weight matched control group (C) receiving dextrose IV and chow orally. Concentration of methyl donor aa was higher in V than in T. On TPN, the animals received 10.2 g of glucose and 3.4 g of aa daily. After TPN, bile flow was measured and hepatocyte membranes were prepared and their composition determined. Results of bile flow and hepatocyte membrane Na+K+ATPase activity are tabulated above : @ = μM Pi/mg prot/h; *= p <.025; **= p <.001; n=6 in each group. Results in C group were similar to V, V+SAMe and T+SAMe. The membrane lipid and protein constituents showed few modifications. Conclusions : the significant decrease of Na+K+ATPase activity indicates an impairment of the bile acid independent flow and membrane fluidity by Travasol which could be restored by the simultaneous administration of SAMe.