title: Dose dependency of the effect of ornithine alpha-ketoglutarate on tissue glutamine concentrations and hypercatabolic response in endotoxaemic rats.
abstract: The optimal dosage of ornithine alpha-ketoglutarate (OKG) for repleting tissue glutamine (Gln) concentrations and maintaining N homeostasis after injury is unknown. We set out to perform 'dose-ranging' of OKG supplementation after an endotoxaemic challenge. Sixty-one male Wistar rats were injected with 3 mg lipopolysaccharide (LPS) from Escherichia coli/kg (n 50) or saline vehicle (9 g NaCl/l; controls n 11). After a 24 h fast, survivors were fed by gavage for 48 h with a polymeric standard diet (879 kJ/kg per d and 1.18 g N/kg per d) supplemented with non-essential amino acids (control, n 11; LPS-OKG-0.0, n 9), or with 0.5 g OKG/kg per d (LPS-OKG-0.5, n 12), 1.5 OKG/kg per d (LPS-OKG-1.5, n 11) or 4.5 g OKG/kg per d (LPS-OKG-4.5, n 10). The diets for all groups were made isonitrogenous with the LPS-OKG-4.5 diet by adding an appropriate amount of non-essential amino acids. Rats were killed on day 3 for blood and tissue sampling (muscle, jejunum mucosa, liver). Urine was collected daily for 3-methylhistidine and total N assays. The OKG dose was correlated with Gln concentrations in every tissue and with cumulative N balance (Spearman test, P<0.01). 3-Methylhistidine excretion was increased in endotoxaemic groups compared with controls (ANOVA, P<0.05) except in the LPS-OKG-4.5 group. Only the LPS-OKG-4.5 group achieved a positive post-injury N balance (t test, P<0.05). In conclusion, OKG exerted a dose-dependent effect on tissue Gln concentration and N balance, but only the highest dosage counteracted myofibrillar hypercatabolism and caused a positive N balance.
authors.affiliation: Service de Biochimie A, Hôpital Saint-Antoine, Paris, France. pascal.pernet@sat.ap-hop-paris.fr
authors.forename: Pascal
authors.initials: P
authors.lastname: Pernet
authors.forename: Colette
authors.initials: C
authors.lastname: Coudray-Lucas
authors.forename: Christina
authors.initials: C
authors.lastname: Schneid
authors.forename: Alain
authors.initials: A
authors.lastname: Jardel
authors.forename: Luc
authors.initials: L
authors.lastname: Cynober
mesh_terms: D000596:Amino Acids / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000378:metabolism* / Q000473:pathology; D005973:Glutamine / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000473:pathology; D008297:Male; D008762:Methylhistidines / Q000652:urine; D009584:Nitrogen / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D009952:Ornithine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000596:Amino Acids; D008070:Lipopolysaccharides; D008762:Methylhistidines; D005973:Glutamine; C002118:ornithine alpha-ketoglutarate; D009952:Ornithine; C028118:3-methylhistidine; D009584:Nitrogen