Weanling Diarrhea

One condition leading to perinatal mortality in the swine and beef industries is “weanling scours,” a diarrheal condition associated with bacterial and viral infection (Lecce et al. 1982). Feeding 0.5% Gln during the weaning period reduced the incidence of diarrhea, and at the gut level, normalized villus and crypt height in the gut while reducing apoptosis (Jagust and Budinger 1992).

Intestinal Injury Associated with Cancer and Immunosuppressant Therapy

In clinical practice, some of the most severe cases of diarrhea occur in patients receiving treatment for cancer. Very strong evidence has been presented for Gln in the preservation and recovery of intestinal structure following radiation injury. Both the villi and crypts are longer with oral Gln (Klimberg et al. 1990; Nambu et al. 1992; Campos et al. 1996), and the effect may be mediated by induction of heme oxygenase-1 (HO-1) (Giris et al. 2006). In a model of radiation-induced intestinal damage, inhibition of HO-1 with zinc protoporphyrin (Giris et al. 2006) or tin mesoporphyrin (Uehara et al. 2005) blocked the protective effect of Gln.

In one of the many studies looking at drug-induced gut injury, Gln reduced injury produced by the immunosuppressant methotrexate, while reducing membrane lipid peroxidation (Gulgun et al. 2010). Arginyl-glutamine dipeptide had similar protective effects (Li et al. 2012).

One intestinal-toxic agent is methionine sulfoximine, an inhibitor of glutamine synthase. Neu’s group was able to produce villous atrophy in artificially fed rat pups via inhibition of Gln synthesis plus withdrawal from luminal Gln. Their procedures resulted in shorter ileal villi and sloughing of microvilli with degeneration of the terminal web (Potsic et al. 2002), and the effects could be reversed with Gln. Note that elevated concentrations of methionine sulfoximine may have other toxic effects than to act as an inhibitor of glutamine synthetase. Results from the rat and pig small intestines indicate the near absence of this enzyme from their mucosae.

Other Models

Other animal models of injury ameliorated or prevented by Gln include traumatic brain injury- associated intestinal damage (Feng et al. 2007), indomethacin injury (Basivireddy et al. 2004), and surgical manipulation injury (Prabhu et al. 2003).

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