Effects of branched-chain amino acid infusion on protein metabolism in rats with acute hepatic failure



Branched-chain amino acids (BCAA) are known to improve hepatic encephalopathy as well as protein malnutrition in cirrhosis. However, such effects in acute hepatic failure (AHF) remain to be elucidated. The current study was conducted to investigate whether BCAA improves protein metabolism in AHF. AHF was induced in male Donryu rats weighing approximately 230 g by giving 60 mg/kg lipopolysaccaride intravenously and 800 mg/kg D-galactosamine hydrochloride intraperitoneally. From 18 hours after injection, AHF rats and control rats were given one of the following five solutions intravenously for 6 hours: (1) saline, (2) 10% glucose, (3) standard 10% amino acid formula with total nitrogen content of 12.2 g/L and BCAA/aromatic amino acid molar ratio of 37.05, (4) BCAA–enriched solution with nitrogen content of 21.9 g/L and the ratio of 148.2, or (5) an active placebo against BCAA-enriched solution with nitrogen content of 21.9 g/L and the ratio of 37.05. In parallel, each group was given a continuous infusion of 14C-leucine. After the plasma radioactivity of 14C-leucine and the expired 14CO2 level reached a plateau, protein turnover was analyzed according to the kinetic model proposed previously by Waterlow. When compared with the control, rates of total protein turnover (total flux), oxidation, and breakdown all increased significantly in AHF. Infusion of standard 10% amino acid formula, BCAA-enriched solution or the placebo in AHF increased total flux and oxidation significantly as compared with the effect of saline or 10% glucose. Although saline, 10% glucose, standard 10% amino acid formula, and the placebo had no effect on synthesis rate, it was increased significantly with BCAA-enriched solution. Breakdown was not suppressed with any solution. These results suggest that rats with AHF are in a catabolic state and that any of the three amino acid solutions can be oxidized to provide energy in AHF. In addition, infusion of BCAA-enriched solution may have a specific protein-sparing effect by increasing the protein synthesis rate even with liver damage. Hence, it is conceivable that infusion of BCAA improves protein metabolism in AHF. (HEPATOLOGY 1995; 22:291–296.)