Prophylactic Administration of Topical Glutamine Enhances the Capability of the Rat Colon to Resist Inflammatory Damage

Abstract

Glutamine is an important nutrient for the GI tract and has been shown to exert a protective effect on the bowel. Nonetheless, in the context of IBD, data demonstrating a therapeutic role for glutamine has been inconclusive. IBD is associated with oxidative stress caused by reactive oxygen species. We aimed to investigate the effect of topical glutamine administration in rats before or after induction of colitis by trinitrobenzenosulfonic acid. In study I glutamine enemas were given beginning 2 days before or on the same day of induction of colitis. Inflammation severity was assessed by macroscopic and microscopic score and tissue myeloperoxidase activity. In study II glutamine enemas were given for 3 days without induction of colitis: mitotic index and colonic crypt length were measured, as well as water-soluble low molecular weight antioxidants and energy-rich phosphate levels (by HPLC). Results showed that glutamine significantly decreased indexes of inflammation when administered before induction of colitis. Glutamine caused an increase in the mitotic index and the levels of water-soluble low molecular weight antioxidants and energy-rich phosphates. We conclude that glutamine exerts a beneficial effect only when administered before induction of colitis, by increasing the resistance of the colonic tissue to inflammatory injury. This effect is probably mediated by increasing the antioxidant capacity and energy level of the tissue.

Potential for amino acids supplementation during inflammatory bowel diseases

“…8 In IBD patients, protein composition such as glutamine enrichment does not influence the effectiveness of enteral nutrition, 9 but studies are still limited. In animals, glutamine protects intestinal mucosa in different models of IBD, i.e., trinitrobenzene sulfonic acid (TNBS), [10][11][12] dextran sulfate sodium (DSS), 13 indomethacin, 14,15 or acetic acid 16 -induced intestinal inflammation. In TNBS-induced colitis, prophylactic treatment (2 weeks) with glutamine decreased bacterial translocation, intestinal lesions, and cytokine (TNFa, IL-8) production.…”

“…10 A shortterm (3-day) prophylactic treatment also limited TNBSinduced intestinal damage. 11,12 Curative treatment with oral glutamine also demonstrated a beneficial effect in an indomethacin model, 14 but failed in a TNBS model. 11,17 These experimental data suggest a beneficial role of glutamine during colitis that could be explained by different mechanisms, summarized in Figure 1.…”

“…52 Glutamine improved intestinal antioxidative defenses like glutathione in different models of injury, 53,54 but it is not yet established in IBD models. 11 Thus, it appears that glutamine is able to downregulate proinflammatory and oxidant responses that contribute to intestinal damage.…”

Effects of glutamine on proinflammatory gene expression and activation of nuclear factor kappa B and signal transducers and activators of transcription in TNBS-induced colitis

“…14 Because enteral glutamine is the main source of amino acids for the enteral mucosa and is metabolized at high rates by enterocytes and immunocytes, 15,16 it has been used in many clinical conditions such as extended trauma or burning, and prolonged fasting and chemotherapy to prevent enteritis and colitis. 17 Although it has been found that glutamine supplementation has no clear benefit in patients with IBD, 18 and there is a report that glutamine enemas fail to improve the inflammatory response in animals receiving TNBS, 19 administration of glutamine by gastric gavage 20,21 or enema 22 before TNBS instillation reduces colonic damage in animals with experimental colitis. Moreover, we have previously reported that glutamine prevents NF-B activation in rats with acetic acid-induced colitis, 1 and it has been recently shown that dietary glutamine improves mucosal function in a dextran sulfate sodium (DSS)-induced model of experimental colitis.…”

Glutamine inhibits cytokine-induced apoptosis in human colonic epithelial cells via the pyrimidine pathway

“…24 and 46). Animal studies of Gln supplementation also suggest gut mucosal cytoprotective effects of this amino acid in chemically-induced IBD, which is associated with increased local cytokine production and (15,18) and accelerated epithelial cell apoptosis (16). Few studies have examined the impact of Gln-derived nucleotides and/or their derivatives themselves on the prevention of intestinal epithelial cell apoptosis.…”