Bacterial dissemination and metabolic changes in rats induced by endotoxemia following intestinal E-coli overgrowth are reduced by ornithine alpha-ketoglutarate administration

The efficacy of ornithine alpha -ketoglutarare (OKG) in preventing bacteria l translocation and dissemination, metabolic disorders and changes in mucos al enzyme activities was assessed in a model of bacterial translocation in rats. Antibiotic decontamination was performed 4 d before intragastric inoc ulation with an Escherichia coil strain (10(10) bacteria/kg body). Two days later, the rats were given either a lipopolysaccharide (LPS) 0127:B8 or a saline injection and were deprived of food for 24 h. Enteral nutrition, [Os molite, 880 kJ/(kg d)] supplemented with either OKG (LPS + OKG) or glycine (Saline + Gly or LPS + Gly), was then given for 2 d. Urinary total nitrogen losses and 3-methylhistidine excretion were determined daily. On killing a t d 3, bacterial translocation to the mesenteric lymph nodes (MLN) and diss emination to the spleen and liver were evaluated, jejunal mucosa enzyme act ivities were assayed and tissue free amino acids in muscles were measured. Endotoxin induced translocation from the gut lumen to the MLN in all groups , whereas dissemination occurred only in LPS-treated rats. OKG significantl y reduced dissemination of the bacteria in the spleen. 3-Methylhistidine ex cretion was greater in the LPS + Gly group (+25%, P < 0.05) than in either the LPS + OKG or Saline + Gly group. The group fed the OKG-enriched diet ha d higher muscular glutamine, ornithine and arginine concentrations than did the Gly-supplemented groups (P < 0.05). Intestinal sucrase and aminopeptid ase activities were higher in the LPS + OKG group than in the LPS + Gly gro up (-30%, P < 0.05). OKG supplementation limits bacterial dissemination and metabolic changes after injury in rats and thus may be useful in the preve ntion of gut-derived sepsis in critically ill patients.