Oral administration of a glutamine-enriched diet before or after endotoxin challenge in aged rats has limited effects.

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

Comparative study of glycine, alanine or casein as inert nitrogen sources in endotoxemic rats.

Pharmacological effects of dietary amino acids (AA) and peptides must be compared to an isonitrogenous control that is as inert as possible. To establish a rationale for the choice of such a control, potential metabolic and nutritional effects of three currently used nitrogenous controls (glycine, alanine, and casein) were evaluated in an endotoxemic rat model that has well-defined alterations in AA and protein metabolism. Five-week-old male Sprague-Dawley rats (113 +/- 1 g) were randomly assigned to four groups and received at d 0 an intraperitoneal injection of endotoxin (3 mg/kg). After withdrawal of food for 24 h, the rats were enterally refed for 48 h with a liquid diet (Osmolite((R))) supplemented with 0.19 g N. kg(-1). d(-1) in the form of glycine [lipopolysaccharide (LPS)-GLY group], alanine (LPS-ALA group) or casein (LPS-CAS group). One group (LPS group) received only Osmolite((R)). Plasma, two skeletal muscles, the liver and the intestine were then removed. Body and tissue weights and tissue protein contents did not differ among the four groups. Intestine histomorphometry showed no significant difference among groups. Jejunal hydrolase activities were significantly affected by the nitrogenous supplementations, but no effect was observed in the ileum. Only limited significant effects were observed on plasma and tissue-free AA concentrations, except for an accumulation of glycine in the plasma and tissues from the LPS-GLY group, compared to other groups. Overall, whereas glycine as a nitrogenous control should be used with care, either alanine or casein may be used as the "placebo," with the choice depending on the study to be performed.

Can a glutamate-enriched diet counteract glutamine depletion in endotoxemic rats?

The study evaluated whether a glutamate-enriched diet would restore glutamine tissue pools and maintain tissue trophicity in endotoxemic rats. For this purpose, young male Sprague-Dawley rats received an intraperitoneal injection of lipopolysaccharide (LPS) from Escherichia coli at 3 mg/kg body weight. After 24 hours of food deprivation, the rats were enterally refed for 48 hours using Osmolite enriched with glutamate at 4 g/kg/d (LPS-Glu group, n = 7) or glycine isonitrogenous to glutamate (LPS-Gly group, n = 7). A control group (healthy group, n = 7) had free access to a standard rodent diet. Tissue weights and protein contents were significantly lower in both LPS-treated groups than in the healthy group. No plasma or tissue accumulation of glutamate was observed except in the liver. Glutamine concentrations were increased in the jejunum, liver, and plasma in the LPS-Glu group versus the other two groups (P < 0.05). Conversely, they were depleted in muscles of the endotoxemic groups versus the healthy group (P < 0.05). Villus height was significantly greater in the LPS-Glu group than in the LPS-Gly group in the jejunum (P < 0.05), but not in the ileum. In conclusion, a glutamate-enriched diet administered enterally to endotoxemic rats can counteract glutamine depletion in the splanchnic area but not in muscles. In addition, glutamate displayed a trophic effect restricted to the jejunum.

A pancreatic extract-enriched diet corrects ileal mucosa atrophy in endotoxemic aged rats.

An altered adaptive response of the pancreas and small intestine to nutritional stress has an adverse impact upon nutritional status in elderly humans or senescent rats. We evaluated the effects of a pancreatic extract nutritional supplement on intestinal mucosa adaptation in LPS-treated aged rats. Endotoxemic rats were starved for 48 hr and then refed ad libitum for four days with a standard diet. Afterwards they received, over one week, the standard diet enriched with either pancreatic extract (PE) (2.4 g/day) or casein (isonitrogenous to PE supplement). Healthy aged rats fed ad libitum with a standard diet were studied in parallel. Whereas no changes occurred in the jejunal segment, an adaptive villus hyperplasia was observed in the proximal ileum of rats receiving PE without an increase in the brush border hydrolase activities. Our results indicate that oral PE supplementation exerts a trophic effect on the ileal mucosa of aged rats in response to nutritional stress.

Supplementation of oral nutrition with pancreatic enzymes improves the nutritional status of aged endotoxemic rats.

Malnutrition is a common problem in elderly people. The association of malnutrition and physical illness or injury leads to both localized and general complications. In particular, impairment of the adaptive response of pancreatic function to undernutrition and refeeding may adversely affect nutritional status and elicit morbidity and mortality. Aged rats (24 mo old) were treated with lipopolysaccharide (LPS) from E. Coli (3 mg/kg body weight). Six days later, survivors were randomized to receive, for 7 days, an oral chow diet enriched with either a pancreatic extract (PE) (2.4 mg/day) or an isonitrogenous supply of casein (CAS). Endotoxemia induced a catabolic state, with a body weight loss of 7.6 +/- 1.1% on day two after LPS treatment. Mean food intake from day 6 to day 13 was similar in LPS-PE and LPS-CAS groups (19.0 +/- 5.6 versus 19.7 +/- 6.9 g). The metabolic response varied according to the type of muscle studied. In fast (white) muscle, the protein content and the glutamine pool remained markedly depleted in endotoxemic rats receiving casein supplementation. In contrast, enrichment of nutrition with PE significantly limited the LPS-induced muscle wasting and increased the muscle glutamine content. As in previous observations, no significant change occurred in slow (red) muscle. These results could indicate that PE supplementation counteracts pancreatic deficiency caused by aging and worsened by stress and this, in turn, could improve the efficiency of nutrition, to support the hypermetabolism of aged injured rats.