The effect of lactitol (NS-4) on the concentrations of ammonia and amino acids in blood and cerebrospinal fluid in Eck fistula (portacaval-shunted) dogs

Abstract

Lactitol and lactulose were compared in their effect on the concentrations of ammonia and amino acids in blood and cerebrospinal fluid (CSF) in Eck fistula dogs. Drugs were administered intragastrically for four weeks from three weeks after the portacaval-shunt operation. The concentration of ammonia in the blood and CSF had increased three to five-fold three weeks after the operation and increased gradually thereafter. Eck fistula dogs showed a characteristic profile of plasma amino acids, with increased concentrations of tryptophan (Trp) and aromatic amino acids (AAA) and reduced concentrations of branched-chain amino acids. The profile of CSF amino acids revealed substantial increases in the concentrations of AAA as well as glutamine (Gln), Trp and glutamic acid. Lactitol at doses of 1 and 3 g/kg/day significantly decreased the ammonia concentration in both the blood and CSF after administration for two and four weeks. Lactitol at a dose of 3 g/kg/day significantly decreased the concentration of Trp in the plasma and the concentrations of valine, leucine, AAA and Gln in CSF. Lactulose showed effects similar to those of lactitol. These findings suggest that lactitol may be a promising agent for the clinical treatment of hyperammonemia and hepatic encephalopathy, since it decreased the concentration of ammonia in the blood and CSF and the elevated concentrations of AAA in CSF associated with the development of hepatic encephalopathy. © 1995, The Japanese Pharmacological Society. All rights reserved.