Cholestatic effect of intraperitoneal administration of tryptophan to suckling rat pups.

The potential cholestatic effect of amino acids and metabolites of tryptophan were evaluated by use of seven daily intraperitoneal injections to suckling and weanling rat pups. Of the amino acids present in parenteral nutrition solutions, only tryptophan (given at a dose of 4 mM/kg) produced a significant (p less than 0.01) elevation of serum cholylglycine (12.8 +/- 1.0 microM/liter) as determined by radioimmunoassay, compared to 4.9 +/- 0.4 microM/liter in saline-treated control animals. Total serum conjugates of cholic acid, as determined by radioimmunoassay, were similarly elevated, as was serum alanine aminotransferase. Tryptophan injection resulted in elevated cholylglycine concentrations only at doses of 3 mM/kg/day or higher. Animals more than 2 weeks old did not demonstrate elevation of serum cholylglycine. Injection of light-exposed tryptophan in suckling animals caused a greater elevation of cholylglycine (39.0 +/- 8.6 microM/liter) than freshly prepared tryptophan solutions (p less than 0.005). Tryptophan and its spontaneous degradation products could contribute to the cholestatic liver changes observed during parenteral nutrition therapy.