Effects of Glutamine Supplements and Radiochemotherapy on Systemic Immune and Gut Barrier Function in Patients With Advanced Esophageal Cancer

Yoshida, Shogo; Matsui, Masasuke; Shirouzu, Yasumasa; Fujita, Hiromasa; Yamana, Hideaki; Shirouzu, Kazuo

doi:10.1097/00000658-199804000-00006

Cited by 94 publications

(49 citation statements)

References 30 publications

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“…25,26 Currently, the SPT is the objective endpoint used in clinical studies to quantify gut damage 12,31 and to assess treatment effects aimed at mucoprotection. 32 By simultaneously using multiple sugar probes, which are chosen on behalf of different permeation pathways, information about intestinal absorptive capacity is obtained in addition to information regarding intestinal permeability. Currently, it is accepted generally that alterations in the L/R ratio provide an index for intestinal permeability, whereas the recovery of RHA, XYL, and OMG and their ratios provide an index the intestinal absorptive capacity.…”

Section: Discussionmentioning

confidence: 99%

Monitoring myeloablative therapy‐induced small bowel toxicity by serum citrulline concentration

Lutgens

Blijlevens

Deutz

et al. 2004

Cancer

141

107

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BACKGROUNDIntestinal mucositis is an important cause of cancer treatment‐related morbidity and mortality, carrying a serious economic burden. Currently, objective parameters are lacking that would enable the monitoring of gut damage in routine clinical practice, thus hindering the development of clinical studies designed to investigate potential new strategies aimed at reducing or preventing this side effect. The authors investigated the characteristics of serum citrulline concentration compared with sugar permeability tests with respect to its use as a marker for cancer treatment‐induced small bowel injury.METHODSIn this prospective study, 10 patients with hematologic malignancies who were receiving myeloablative therapy had gut toxicity assessed with sugar permeability tests. Serum citrulline concentrations also were determined using archival serum samples. The association between both parameters and their respective characteristics were analyzed and compared with data from the literature.RESULTSSensitivity and specificity were better for the citrulline assay compared with sugar permeability tests. Maximum gut damage assessed with the citrulline assay was observed 1–2 weeks earlier compared with the sugar permeability test. Similarly, citrulline indicated recovery of gut damage at 3 weeks after transplantation, whereas most sugar permeability tests remained abnormal.CONCLUSIONSThe simplicity of the method, the low costs, and the lack of drawbacks to the method make the citrulline assay the first choice for measuring and monitoring treatment‐related gut damage and provides an objective parameter for cancer treatment‐related gut toxicity. Cancer 2005. © 2004 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Monitoring myeloablative therapy‐induced small bowel toxicity by serum citrulline concentration

Lutgens

Blijlevens

Deutz

et al. 2004

Cancer

141

107

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“…3), whereas apical or basolateral glutamine supplementation decreased permeability. Because of its role in the preservation of gut integrity (46,49), it was proposed that altered glutamine metabolism and loss of gut barrier function were related to disturbed proliferation or differentiation of enterocytes (12,42). Others postulated that fasting (23) and glutamine deprivation (37) induce apoptosis in intestinal epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Glutamine preserves protein synthesis and paracellular permeability in Caco-2 cells submitted to ”luminal fasting“

Bacquer

Laboisse

Darmaun

2003

American Journal of Physiology-Gastrointestinal and Liver Physi

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Le Bacquer, Olivier, Christian Laboisse, and Dominique Darmaun. Glutamine preserves protein synthesis and paracellular permeability in Caco-2 cells submitted to "luminal fasting." Am J Physiol Gastrointest Liver Physiol 285: G128-G136, 2003; 10.1152/ajpgi.00459.2002.-This study used polarized cell line Caco-2 as a model of human enterocytes to determine: 1) whether deprivation of nutrients on the apical (luminal) side of the epithelium (fasting) alters protein synthesis in enterocytes; 2) if so, whether glutamine can attenuate the effects of fasting; and 3) whether the effects of glutamine depend on its route (i.e., apical vs. basolateral) of supply. Caco-2 cells were submitted to nutrient deprivation on the apical side to mimic the effects of fasting, whereas the basolateral side of the epithelium remained exposed to regular medium. Cells were then incubated with [ 2 H3]leucine with or without glutamine, and the fractional synthesis rate (FSR) of total cell protein was determined from [ 2 H3]leucine enrichments in protein-bound and intracellular free leucine measured by gas chromatography/mass spectrometry. A 24-h apical nutrient deprivation (luminal fasting) was associated with a decline in intracellular glutamine, glutamate, and glutathione concentrations (Ϫ38, Ϫ40, and Ϫ40%, respectively), protein FSR (Ϫ20%), and a rise in passage of dextran, an index of transepithelial permeability. In fasted cells, basolateral or luminal glutamine supplementation did not alter the glutathione pool, but it restored protein FSR and improved permeability. The effects of glutamine were abolished by 6-diazo-oxo-L-norleucine, an inhibitor of glutaminase, and was mimicked by glutamate. We conclude that in Caco-2 cells, protein synthesis depends on nutrient supply on the apical side, and glutamine regardless of the route of supply corrects some of the deleterious effects of fasting in a model of human enterocytes through its deamidation into glutamate. stable isotopes; leucine; small intestine; gut trophicity; human enterocyte

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“…In addition, in vivo experiments were performed to corroborate the inhibition of TxA-induced apoptosis by both glutamine and alanyl-glutamine. Significant effects of glutamine on preventing the intestinal damage induced by radiation (53) or chemotherapy (10,55), as well as the effects of glutamine in driving sodium absorption in cholera (25) and cryptosporidium-induced diarrhea (2), provided a strong rationale. Both glutamine and alanyl-glutamine significantly reduced the welldocumented intestinal damage caused by TxA in rabbit ileal loops and reduced the amount of epithelial-cell apoptosis.…”

Section: Vol 74 2006 Glutamine and Its Derivative Inhibit Toxin A Ementioning

confidence: 99%

“…Glutamine (Gln) is a major respiratory fuel for the intestinal epithelium (50), and its supplementation is efficacious in repairing intestinal mucosal injury caused chemotherapeutic agents (55) and radiation (53), as well as in driving NaCl absorption in experimental models of infectious diarrhea, such as cholera (42), cryptosporidiosis (2), and rotavirus enteritis (36). These actions support the use of glutamine as a therapeutic adjuvant in infectious diarrhea (9) and catabolic stressful conditions (i.e., cancer chemotherapy, prolonged parenteral nutrition, sepsis, and human immunodeficiency virus-related wasting syndrome) (7,12,41,55).…”

mentioning

confidence: 99%

Caspase and Bid Involvement inClostridium difficileToxin A-Induced Apoptosis and Modulation of Toxin A Effects by Glutamine and Alanyl-Glutamine In Vivo and In Vitro

Carneiro

Fujii

Brito³

et al. 2006

Infect Immun

102

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Clostridium difficile is the leading cause of nosocomial bacterial diarrhea. Glutamine and its stable and highly soluble derivative alanyl-glutamine, have been beneficial in models of intestinal injury. In this study, we extend our work on the mechanisms of Clostridium difficile toxin A (TxA)-induced apoptosis in human intestinal epithelial T84 cells and evaluate the effects of glutamine and alanyl-glutamine on TxA-induced apoptosis in vitro and disruption of ileal mucosa in vivo. T84 cells were incubated with TxA (100 ng/ml) in medium with or without glutamine or alanyl-glutamine (3 to 100 mM). Apoptosis was evaluated by DNA fragmentation in vitro and the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling method in vivo. Caspase and Bid involvement were investigated by Western blotting. Ligated rabbit ileal loops were used for the evaluation of intestinal secretion, mucosal disruption, and apoptosis. TxA induced caspases 6, 8, and 9 prior to caspase 3 activation in T84 cells and induced Bid cleavage by a caspase-independent mechanism. Glutamine or alanyl-glutamine significantly reduced TxA-induced apoptosis of T84 cells by 47% and inhibited activation of caspase 8. Both glutamine and alanyl-glutamine reduced TxA-induced ileal mucosal disruption and secretion. Altogether, we further delineated the apoptosis-signaling cascade induced by TxA in T84 cells and demonstrated the protective effects of glutamine and alanyl-glutamine. Glutamine and alanyl-glutamine inhibited the apoptosis of T84 cells by preventing caspase 8 activation and reduced TxA-induced intestinal secretion and disruption.

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Effects of Glutamine Supplements and Radiochemotherapy on Systemic Immune and Gut Barrier Function in Patients With Advanced Esophageal Cancer

Cited by 94 publications

References 30 publications

Monitoring myeloablative therapy‐induced small bowel toxicity by serum citrulline concentration

Monitoring myeloablative therapy‐induced small bowel toxicity by serum citrulline concentration

Glutamine preserves protein synthesis and paracellular permeability in Caco-2 cells submitted to ”luminal fasting“

Caspase and Bid Involvement inClostridium difficileToxin A-Induced Apoptosis and Modulation of Toxin A Effects by Glutamine and Alanyl-Glutamine In Vivo and In Vitro

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