Total parenteral nutrition‐associated cholestasis in rats: comparison of different amino acid mixtures

Abstract

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.

Association between Hydrogen Peroxide-Dependent Byproducts of Ascorbic Acid and Increased Hepatic Acetyl-CoA Carboxylase Activity

“…The etiology of TPNrelated steatosis is multifactorial (2 ), and many nutritional elements have been suspected, such as an amino acid imbalance (3)(4)(5)(6), an excess of glucose or lipids (7 ), or a carbohydrate/nitrogen ratio imbalance (8 ). Oxidative stress (1, 9 -11 ) and products derived from photooxidation of amino acids (9,12 ) have also been proposed.…”

Photooxidation of Parenteral Multivitamins Induces Hepatic Steatosis in a Neonatal Guinea Pig Model of Intravenous Nutrition

“…TPN-related hepatic dysfunctions (25) have been linked to oxidant stress (26,27) as well as genetic (28,29), nutritional, environmental, and inflammatory factors (23). More specifically, the following nutritional factors have been associated with steatosis and/or cholestasis: enteral starvation (30,31), an amino acid imbalance (32,33), photo-oxidized products of amino acids (11,12,34), an excessive infusion of glucose (35) or lipids (36), a carbohydrate to nitrogen imbalance (37,38), and the source of infused lipids (39).…”

Entéropathies congénitales et transplantation intestinale

“…(6) Les apports excessifs en acides gras polyinsaturés à longue chaîne avec lipoperoxydation secondaire [53,54] et la teneur élevée en phytostérols des émulsions à base d'huile de soja [55].…”

“…(a) La limitation des apports en glucose afi n de rédui-re l'accumulation hépatique de lipides [62,63] , et (b) L'utilisation du type et de la quantité appropriés d'émulsion lipidique intraveineuse pour apporter les acides gras essentiels, réduire la charge en glucose et limiter la peroxydation [53][54][55] . Des émulsions lipidiques à base d'huile d'olive récemment développées peuvent réduire la peroxydation [54] .…”

“…(6) Au contrôle des apports en lipides et du débit de leur administration et/ou à l'arrêt des lipides intraveineux dès la survenue d'une thrombopénie, d'une hyperbilirubinémie et/ou d'un ictère [53] .…”