Effect of dichloroacetate on plasma and hepatic amino acids in sterile inflammation and sepsis.
The effect of sterile inflammation and chronic sepsis on the plasma and hepatic free amino acid concentrations was determined. Relative to control animals, only minor alterations in the plasma amino acid concentrations were observed in sterile inflammation and sepsis. In liver, concentrations of alanine, serine, threonine, asparagine, proline, and glycine were significantly increased to the same extent in sterile inflammation and sepsis, while hepatic glutamine concentrations were significantly decreased. Compared with sterile inflammation, the branched-chain amino acid concentrations were depressed in the liver of septic animals. Following administration of dichloroacetate, hepatic alanine concentrations were significantly reduced more than threefold in each of the conditions examined; in contrast, significant increases in hepatic concentrations of threonine, glycine, glutamine, glutamate, histidine, and proline were observed. Also following administration of dichloroacetate, the branched-chain amino acid concentrations were all significantly elevated in each of the conditions examined, and plasma alanine concentrations were significantly decreased, while those of glutamine and glycine were significantly increased. These results demonstrate that there is a disassociation between the plasma and hepatic concentration of free amino acids in sterile inflammation and sepsis. Furthermore, the results demonstrate that some of the alterations in hepatic amino acid metabolism may be reversed pharmacologically by dichloroacetate.
Vary
T C
TC
Maryland Institute for Emergency Medical Services Systems, University of Maryland School of Medicine, Baltimore.
Siegel
J H
JH
Placko
R
R
Tall
B D
BD
Morris
J G
JG
D000038:Abscess / Q000378:metabolism*; D000085:Acetates / Q000494:pharmacology*; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001442:Bacteroides Infections / Q000378:metabolism*; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004927:Escherichia coli Infections / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010538:Peritonitis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000085:Acetates; D000596:Amino Acids; D003999:Dichloroacetic Acid