Glutamine Supplementation and Deprivation: Effect on Artificially Reared Rat Small Intestinal Morphology

Abstract

The mechanisms of how glutamine benefits critically ill patients have not been established. The purpose of this study was to determine the effects of dietary and endogenously produced glutamine on small intestinal morphology using light and transmission electron microscopy in artificially reared rat pups. It was hypothesized that deprivation of dietary glutamine leads to intestinal disease that is exacerbated by inhibition of glutamine synthetase by methionine sulfoximine (MS). Rat pups were placed into five different test groups: The first was a reference group that was reared by their mother. The other four groups were reared artificially and received a 10% Travasol amino acid solution at 5 g/kg per day, which does not contain glutamine, added to a mixture containing carbohydrates, lipids, and vitamins. This dose was chosen because it represents an approximation of the amount of glutamine these rats would be receiving in a normal rat diet (approximately 40 g/kg per day total protein, 10 to 15% of which is glutamine + glutamate). The glutamine was manipulated by adding glutamine (Q) or MS or both. The four groups were as follows: MS-Q-, MS-Q+, MS+Q-, and MS+Q+. Light microscopy revealed the greatest blunting of villus height in the ileum of rats from the MS+Q- group when compared with the MS-Q+ group (123 +/- 48.9 micro m versus 207 +/- 36 microm, p < 0.05). The other two groups exhibited intermediate villus heights, but all were shorter than the villi from the mother-reared animals. The number of villi per unit length of bowel was also lowest in the animals that were treated with MS and not provided with dietary glutamine. Transmission electron microscopy demonstrated breakdown of the epithelial junctions in the glutamine-deprived and glutamine synthetase-inhibited intestines. Glutamine-deprived animals also displayed sloughing of microvilli, decreased actin cores, and degeneration of the terminal web. In summary, these studies support the hypothesis that glutamine is involved with maintenance of intestinal epithelial integrity.

Morphology of the Intestinal Barrier in Different Physiological and Pathological Conditions

“…Electron microscopy of the intestine in a GLN-deprived infant rat model demonstrated intestinal intercellular junction breakdown [36].…”

Validation of the gastroschisis experimental model and the influence of the mother's diet enriched with glutamine in the fetal morphology

“…In literature, the used dosages vary, not being possible to find a standard or a consensus about the proper data of glutamine in experimental animals. It is seen in the studies empiric supplementation in newborn, varying from 0.2 to 4gr/kg of weight /day 17,19 . This way, new researches have to be done to check if the used dosages in this study were not enough and in that way have not changed the macroscopic intestine parameters of the fetuses.…”

Neonatal Formula Feeding Leads to Immunological Alterations in an Animal Model of Type 1 Diabetes

“…At 7 d of age, pups were randomized to the exclusively MF model or to the pup-in-the-cup model feeding with a prepared formula, based on the composition of rat milk, but lacking host defense factors such as immunoglobulin and antibacterial peptides (rat milk substitute (RMS)) (12). Under isoflurane anesthesia, feeding tubes constructed from 14-cm sections of polyethylene tubing were inserted into the stomach as previously described (13). All pups underwent anesthesia and gastrostomy placement, but the MF group was returned to their mothers, and the RMS group received formula feeding.…”