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Articles

Bacterial Dissemination and Metabolic Changes in Rats Induced by Endotoxemia following Intestinal E. coli Overgrowth Are Reduced by Ornithine -Ketoglutarate Administration¹

Laurent Schlegel^*,, Colette Coudray-Lucas^*,, Frédéric Barbut^**, Jacques Le Boucher^*, Alain Jardel, Setareh Zarrabian and Luc Cynober^,2

^* INSERM U402, Faculté de médecine Saint-Antoine, 75012 Paris, France; Laboratoire de Biologie de la Nutrition, E.A. 2498, Faculté de Pharmacie, 75270 Paris Cedex 06-France; ^** Laboratoire de bactériologie, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France; Laboratoire de physiologie humaine, UFR de Pharmacie, 49000 Angers, France; INSERM U458, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, 75019 Paris, France; and INSERM U341, Hôtel-Dieu, 75181 Paris Cedex 04-France

²To whom correspondence should be addressed.

The efficacy of ornithine -ketoglutarate (OKG) in preventing bacterial translocation and dissemination, metabolic disorders and changes in mucosal enzyme activities was assessed in a model of bacterial translocation in rats. Antibiotic decontamination was performed 4 d before intragastric inoculation with an Escherichia coli strain (10¹⁰ 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, [Osmolite, 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 at d 3, bacterial translocation to the mesenteric lymph nodes (MLN) and dissemination to the spleen and liver were evaluated, jejunal mucosa enzyme activities 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 significantly reduced dissemination of the bacteria in the spleen. 3-Methylhistidine excretion 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 had higher muscular glutamine, ornithine and arginine concentrations than did the Gly-supplemented groups (P < 0.05). Intestinal sucrase and aminopeptidase activities were higher in the LPS + OKG group than in the LPS + Gly group (-30%, P < 0.05). OKG supplementation limits bacterial dissemination and metabolic changes after injury in rats and thus may be useful in the prevention of gut-derived sepsis in critically ill patients.

KEY WORDS: • ornithine -ketoglutarate • endotoxemia • bacterial translocation • protein catabolism • rats