It has been suggested that the quantity of amino acids perfused is a pathogenetic factor in total parenteral nutrition (TPN)-associated hepatotoxicity. However, the effect of the qualitative pattern of amino acid solutions has not been studied. Rats on parenteral nutrition for 5 days received 10.2 g of dextrose and 3.4 g of amino acids daily. Bile flow (microliter/min/g liver protein) after administration of Vamin was 16.2 +/- 0.8, which was similar to that in controls given chow and dextrose iv, but it was significantly higher (p less than 0.001) than those on Travasol (12.3 +/- 0.8). The decrease in bile flow was not related to the large concentrations of alanine and glycine present in Travasol. However, the addition to Travasol of serine present only in Vamin increased bile flow significantly. Bile acid secretion rate, biliary lipid constituents, calcium, sodium, and glucose showed little change. In contrast, alpha-amino nitrogen was increased (p less than 0.05) in Vamin-perfused animals. Steatosis was noted in only a few animals in the Travasol group, and was not associated with an increase in the triglycerides content of the liver. Glycogen and protein content of the livers did not differ. The data show that the composition of amino acid solutions may be a determinant of TPN-induced cholestasis and suggest that the presence of methyl donor amino acids may have a protective effect.
In vivo studies were carried out in young Sprague-Dawley rats to examine the role of gastric lipolysis on fat absorption and bile acid metabolism. When fed by gastric perfusion 5 times (corn oil, 4 g/day) their usual dietary intake of fat, rats deprived of lingual lipase by the creation of an esophageal fistula had a significant degree of fat and bile acid malabsorption as well as a shortened bile acid half-life when compared to animals with a gastrostomy. The % fat absorption, bile acid loss and bile acid pool were normal in 2 groups of esophageal fistula rats fed the same quantity of corn oil or twice (8 g/day) that amount as a fine emulsion. In view of a negligible gastric lipase activity in animals with an esophageal fistula and of decreased hydrolysis of a triglyceride test meal, these data suggest that gastric lipolysis is of physiological importance in situations where lipolytic mechanisms are stressed by a large fat intkae. Its principal role is to potentiate intestinal lipolysis by facilitating the emulsification of dietary lipids through its formed products and, therefore, the contact of pancreatic lipase with its substrates.
~ The present study was aimed at determining whether the protection by taurine of lithocholate-sulfate-induced cholestasis is mediated by conjugation or by direct effect of the amino acid on bile formation. Injection of free and conjugated (glycine and taurine) sulfated lithocholate in guinea pigs significantly reduced the secretion rate of non-sulfated bile acids in bile. There was no decrease in bile flow after the injection of taurine-conjugated sulfated lithocholate, which was completely recovered in bile within 60 min. In contrast, injection of sulfated lithocholate and its glycine conjugate led to a marked decrease in bile flow, and neither one was significantly recovered in bile. In addition, both caused morphological changes in the liver, characterized by the accumulation of cytoplasmic vacuoles with lamellated myelin figures characteristic of phospholipidosis. Pretreatment with taurine (0.5% in drinking water for 3 days) prevented both the drop in bile flow and the histological changes in the liver, suggesting that conjugation with taurine removed the cholestatic potential of sulfated lithocholate. However, since taurine was effective not only in preventing cholestasis induced by the free form of sulfated lithocholate but also against its glycine conjugate, these results suggest that other mechanisms in addition to conjugate must be involved.
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