Glutamate reduces experimental intestinal hyperpermeability and facilitates glutamine support of gut integrity

AIM:To assess whether glutamate plays a similar role to glutamine in preserving gut wall integrity.METHODS:The effects of glutamine and glutamate on induced hyperpermeability in intestinal cell lines were studied.Paracellular hyperpermeability was induced in Caco2.BBE and HT-29CL.19A cell lines by adding phorbol-12,13-dibutyrate(PDB) apically,after which the effects of glutamine and glutamate on horseradish peroxidase(HRP) diffusion were studied.An inhibitor of glutamate transport(L-trans-pyrrolidine-2,4-dicarboxylic acid:trans-PDC) and an irreversible blocker(acivicin) of the extracellular glutamine to glutamate converting enzyme,γ-glutamyltransferase,were used.RESULTS:Apical to basolateral HRP flux increased significantly compared to controls not exposed to PDB (n=30,P<0.001).Glutamine application reduced hyperpermeability by 19%and 39%in the respective cell lines.Glutamate application reduced hyperpermeability by 30%and 20%,respectively.Incubation of HT29CL.19A cells with acivicin and subsequent PDB and glutamine addition increased permeability levels.Incubation of Caco2.BBE cells with trans-PDC followed by PDB and glutamate addition also resulted in high permeability levels.CONCLUSION:Apical glutamate-similar to glutaminecan decrease induced paracellular hyperpermeability.Extracellular conversion of glutamine to glutamate and subsequent uptake of glutamate could be a pivotal step in the mechanism underlying the protective effect of glutamine.

Antioxidant enriched enteral nutrition and oxidative stress after major gastrointestinal tract surgery

AIM: To investigate the effects of an enteral supple-ment containing antioxidants on circulating levels of antioxidants and indicators of oxidative stress after major gastrointestinal surgery.METHODS: Twenty-one patients undergoing major upper gastrointestinal tract surgery were randomised in a single centre, open label study on the effect of postoperative enteral nutrition supplementedwith antioxidants. The effect on circulating levels of antioxidants and indicators of oxidative stress, such as F2-isoprostane, was studied. RESULTS: The antioxidant enteral supplement showed no adverse effects and was well tolerated. After surgery a decrease in the circulating levels of antioxidant parameters was observed. Only selenium and glutamine levels were restored to pre-operative values one week after surgery. F2-isoprostane increased in the first three postoperative days only in the antioxidant supplemented group. Lipopolysaccharide binding protein (LBP) levels decreased faster in the antioxidant group after surgery.CONCLUSION: Despite lower antioxidant levels there was no increase in the circulating markers of oxidative stress on the first day after major abdominal surgery. The rise in F2-isoprostane in patients receiving the antioxidant supplement may be related to the conversion of antioxidants to oxidants which raises questions on antioxidant supplementation. Module AOX restored the postoperative decrease in selenium levels. The rapid decrease in LBP levels in the antioxidant group suggests a possible protective effect on gut wall integrity. Further studies are needed on the role of oxidative stress on outcome and the use of antioxidants in patients undergoing major abdominal surgery.