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 ϩ glutamate). The glutamine was manipulated by adding glutamine (Q) or MS or both. The four groups were as follows: MSϪQϪ, MSϪQϩ, MSϩQϪ, and MSϩQϩ. Light microscopy revealed the greatest blunting of villus height in the ileum of rats from the MSϩQϪ group when compared with the MSϪQϩ group (123 Ϯ 48.9 m versus 207 Ϯ 36 m, p Ͻ 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. Previous studies have found that glutamine supplementation significantly decreases morbidity among critically ill patients. Adult bone marrow transplant recipients who received glutamine i.v. had significant decreases in length of hospital stay, hospital-acquired sepsis, and hospital costs (1, 2). Studies in VLBW infants found that glutamine supplementation resulted in decreased morbidity and hospital costs (3-5). Additionally, studies in rodents found that glutamine supplementation provides protection against sepsis and subsequent distal organ damage (6, 7). The mechanisms of how glutamine acts to promote these beneficial effects are not known. However, there is evidence that its effect on intestinal mucosal integrity may play a role. The addition of glutamine to TPN has been demonstrated to maintain the integrity of small intestinal mucosa, therefore, preventing the atrophy typically noted with TPN (8). In a previous study of multiple animal species, administration of glutaminase decreased plasma g...

Necrotizing Enterocolitis

“…[117] acid. Using a bacterial pathogenesis model of reared rats, Potsic et al [127] have shown the role of glutamine in the necrotizing enterocolitis in weanling rabbits, we have shown that maintenance of intestinal epithelial integrity. Instituting supplementation and deprivation in artificially necrotizing enterocolitis.…”

Effects of glutamine on wound healing

“…However, daily protein intake at old ages should be higher because of the decrease in the ability of body for protein synthesis (1). Wound healing can be effected negatively in the presence of factors that increase collagen synthesis such as chronic malnutrition, diabetes mellitus, uraemia and advanced age (3,13). Therefore, in such cases, to increase wound healing, the requirement for the replacement of molecules like Gln, Arg and HMB that increase collagen synthesis cannot be denied.…”

Effects of dietary glutamine supplementation on growth performance, antioxidant status and intestinal function in juvenile grass carp (Ctenopharyngodon idella)

“…For example, dietary supplementation with Gln can improve nutrition status in weanling piglets by preventing intestinal dysfunction and atrophy (Wang et al, ). Gln supplementation also has an effect on artificially reared rat small intestinal morphology, playing an important role in the maintenance of intestinal epithelial integrity (Potsic et al, ). Gln supplementation also affected the growth performance and small intestinal morphology of hatchling broilers, as a 1 g/kg Gln diet improved weight gain, feed efficiency and livability (Yi, Allee, Knight, & Dibner, ).…”