Enteral administration of ornithine alpha-ketoglutarate or arginine alpha-ketoglutarate: a comparative study of their effects on glutamine pools in burn-injured rats.
OBJECTIVE
Ornithine alpha-ketoglutarate has proved to be an efficient nutritional support in trauma situations, especially after burn injury. To determine whether the action of ornithine alpha-ketoglutarate is due to its alpha-ketoglutarate moiety (as a glutamine precursor), we studied the effects of alpha-ketoglutarate administered to rats as ornithine alpha-ketoglutarate, or in combination with arginine salt (arginine alpha-ketoglutarate), as the two closely related amino acids have similar metabolic behavior.


METHODS
Prospective, randomized trial.


METHODS
Animal laboratory.


METHODS
Forty-six male Wistar rats, weighing approximately 90 g.


METHODS
Rats were burned over 20% of their body surface area, starved for 24 hrs, with water ad libitum, and then enterally refed for 48 hrs using Osmolite (210 kcal/kg/day, 1.2 g of nitrogen/kg/day), supplemented with one of the following: a) an amount of glycine isonitrogenous to ornithine alpha-ketoglutarate (group 1); b) 5 g of monohydrated ornithine alpha-ketoglutarate/kg/day (group 2); c) an amount of arginine alpha-ketoglutarate isonitrogenous to ornithine alpha-ketoglutarate (group 3); or d) an amount of arginine alpha-ketoglutarate isomolar to ornithine alpha-ketoglutarate (group 4).


RESULTS
We measured amino acid concentrations in plasma, muscle, and liver, and plasma urea concentration. At refeeding, ornithine alpha-ketoglutarate increased plasma glutamine concentration (p < .05 vs. the three other groups), and counteracted the increase in plasma phenylalanine concentration. In muscle, although the three alpha-ketoglutarate combinations induced similar increases in the glutamate pool, ornithine alpha-ketoglutarate induced the highest increase in glutamine (7.0 +/- 0.3 vs. 5.4 +/- 0.3 micromol/g in group 3, 6.3 +/- 0.3 in group 4, and 4.6 +/- 0.2 in group 1, p < .01 between group 2 and groups 3 or 1). Also, only ornithine alpha-ketoglutarate increased liver glutamine concentration. Finally, isomolar arginine alpha-ketoglutarate increased plasma urea concentration (+50% vs. the three other groups, p < .01).


CONCLUSIONS
Our results demonstrate, for the first time, the following: a) the action of ornithine alpha-ketoglutarate as a glutamine precursor cannot solely be ascribed to alpha-ketoglutarate since arginine alpha-ketoglutarate combinations did not exhibit this effect to the same extent; and b) the action of ornithine alpha-ketoglutarate is not due to its nitrogen content since isonitrogenous arginine alpha-ketoglutarate did not reproduce the effects of ornithine alpha-ketoglutarate.
Le Boucher
J
J
Departement de Physiologie, UER des Sciences Pharmaceutiques et Biologiques, Chatenay-Malabry, France.
Coudray-Lucas
C
C
Lasnier
E
E
Jardel
A
A
Ekindjian
O G
OG
Cynober
L A
LA
D000596:Amino Acids / Q000097:blood*; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002056:Burns / Q000378:metabolism*; D004750:Enteral Nutrition; D005973:Glutamine / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D009952:Ornithine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D007656:Ketoglutaric Acids; D005973:Glutamine; C002118:ornithine alpha-ketoglutarate; D001120:Arginine; D009952:Ornithine