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Article

Oral Administration of a Glutamine-Enriched Diet Before or After Endotoxin Challenge in Aged Rats Has Limited Effects¹

Marie-Chantal Farges^*2, Marie-Pierre Bérard^*, Francis Raul, Jean-Pierre Cézard, Bernard Joly^§, Paule Davot^*, Marie-Paule Vasson^* and Luc Cynober^*

^* Laboratoire de Biochimie, Biologie Moléculaire et Nutrition EA 2416, Faculté de Pharmacie et Centre de Recherche en Nutrition Humaine, 28 place Henri Dunant, BP 38, 63001 Clermont-Ferrand, France, IRCAD CJF INSERM 95-09, 1 place de l'Hôpital Civil, BP 426, 67091 Strasbourg, France, INSERM U458, Hôpital Robert Debré, 48 boulevard Sérurier, 75935 Paris cedex 19, France, and ^§ Laboratoire de Bactériologie, Faculté de Pharmacie, 28 place Henri Dunant, BP 38, 63001 Clermont-Ferrand, France

² To whom correspondence should be addressed.

Numerous studies indicate beneficial effects of glutamine (Gln) in many models of catabolic adult rats. No data were available for aged rats. The effects of oral L-Gln-enriched diet were tested in endotoxemic 24-mo old rats. First, rats received for 7 d (from d0 to d7) an oral diet supplemented with either L-Gln [1g/(kg · d)] or casein (Cas: isonitrogenous supply) prior to lipopolysaccharide (LPS) challenge. The rats were then killed after 24 h food deprivation (from d7 to d8). Endotoxemia induced a catabolic response as shown by muscle glutamine depletion, hyperphenylalaninemia, small bowel atrophy and impaired functionality and bacterial translocation. The Gln-enriched diet did not prevent muscle Gln depletion but significantly (P 0.05) enhanced plantaris protein content by 18% compared to the Cas-LPS rats and reduced the plasma phenylalanine-to-tyrosine ratio (1.32 ± 0.05 vs. 1.54 ± 0.10, respectively, P 0.01). Gut translocation and histomorphology were unaffected by diet. However, Gln pretreatment reduced the fall in sucrase and glucoamylase activities in the ileum, respectively, by 55 and 63% vs. Cas supplementation (P 0.05). In a second study, after endotoxin challenge, healthy 24-mo-old rats were then food-deprived for 2 d (from d0 to d2), received a nonpurified diet for 4 d (from d2 to d6), and then Cas or L-Gln-supplemented diet for 7 d (from d6 to d13). No beneficial effects of Gln supplementation were observed except an increase of 50 and 56% in sucrase and glucoamylase activities in the ileum of Gln-treated rats, (P 0.01 vs. healthy rats). In conclusion, the effects of L-Gln supplementation in aged endotoxemic rats were limited.

KEY WORDS: • aged rats • Gln-supplemented diet • endotoxemia • amino acids • muscles • small bowel