A Diet Containing Whey Protein, Glutamine, and TGFβ Modulates Gut Protein Metabolism During Chemotherapy-Induced Mucositis in Rats

Boukhettala, Nabile; Ibrahim, Ayman; Claeyssens, Sophie; Faure, Magali; Pessot, Florence Le; Vuichoud, Jacques; Lavoinne, Alain; Breuillé, Denis; Déchelotte, Pierre; Coëffier, Moı̈se

doi:10.1007/s10620-009-1039-2

Cited by 17 publications

(15 citation statements)

References 33 publications

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“…The variance in observed individual signs of mucositis could be a result of genetic variability between outbred Wistar rats (30). Also, our mucositis model is based upon a single intravenous injection of MTX, leaving the period of epithelial crypt cell susceptibility to MTX shorter than in models where multiple MTX injections are used (4,10,13,28,29). The amount of subsequent crypt loss by apoptosis, crypt atrophy, and ultimately villus atrophy (39) therefore differs per MTX-injected rat.…”

Section: Discussionmentioning

confidence: 99%

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Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model

Fijlstra

Rings

Verkade

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Fijlstra M, Rings EH, Verkade HJ, van Dijk TH, Kamps WA, Tissing WJ. Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model. Am J Physiol Gastrointest Liver Physiol 300: G283-G291, 2011. First published November 18, 2010 doi:10.1152/ajpgi.00462.2010.-Patients with chemotherapy-induced gastrointestinal mucositis suffer from anorexia, diarrhea, and stomach pain, often causing weight loss and malnutrition. When the intestinal function during mucositis would be known, a rational feeding strategy might improve the nutritional state, accelerate recuperation, and increase survival of mucositis patients. We developed a methotrexate (MTX)-induced mucositis rat model to study nutrient digestion and absorption. To determine lactose digestion and absorption of its derivative glucose during mucositis, we injected Wistar rats intravenously with MTX (60 mg/kg) or 0.9% NaCl (controls). Four days later, we orally administered trace amounts of [1-13 C]lactose and [U-13 C]glucose and quantified the appearance of labeled glucose in the blood for 3 h. Finally, we determined plasma citrulline level and harvested the small intestine to assess histology, myeloperoxidase level, glycohydrolase activity, immunohistochemical protein, and mRNA expression. MTX-treated rats showed profound villus atrophy and epithelial damage. During the experimental period, the absorption of lactose-derived [1-13 C]glucose was 4.2-fold decreased in MTXtreated rats compared with controls (P Ͻ 0.01). Lactose-derived [1-13 C]glucose absorption correlated strongly with villus length (rho ϭ 0.86, P Ͻ 0.001) and with plasma citrulline level (rho ϭ 0.81, P Ͻ 0.001). MTX treatment decreased jejunal lactase activity (19.5-fold, P Ͻ 0.01) and immunohistochemical protein and mRNA expression (39.7-fold, P Ͻ 0.01) compared with controls. Interestingly, MTX treatment did not affect the absorption of [U-13 C]glucose during the experimental period. We conclude that lactose digestion is severely decreased during mucositis while glucose absorption is still intact, when supplied in trace amounts. Plasma citrulline level might be a useful objective, noninvasive marker for lactose maldigestion during mucositis in clinic.

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Section: Discussionmentioning

confidence: 99%

“…Lactose digestion and absorption of its derivative [1][2][3][4][5][6][7][8][9][10][11][12][13] C]-glucose. Blood appearance of lactose-derived [1-13 C]glucose was determined over a 3-h period after bolus administration.…”

Section: The Lactose Digestion and Glucose Absorption Testmentioning

confidence: 99%

Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model

Fijlstra

Rings

Verkade

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…These findings are complemented by evidences showing that a diet containing whey proteins modulates gut nitrogen metabolism in rats with mucositis (Boukhettala et al, 2010) and could be involved in anti-inflammatory properties (Kanwar & Kanwar, 2009). Indeed, casein, beta-casomorphins, whey proteins or their peptide hydrolisates have demonstrated effects on gastrointestinal motility (Daniel et al, 1990), gastric secretion and enterogastrone response (Calbet & Holst, 2004) or anorexigenic hormones (Diepvens et al, 2008).…”

Section: Discussionmentioning

confidence: 81%

A regular curd consumption improves gastrointestinal status assessed by a randomized controlled nutritional intervention

Navas-Carretero¹,

Abete²,

Cuervo³

et al. 2013

International Journal of Food Sciences and Nutrition

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“…Nutritional drinks enriched with transforming growth factor β (TGF-β), free l -glutamine, short-chain fatty acids (SCFAs) and whey proteins have been studied in a number of animal models, and have largely demonstrated protection against chemotherapy-induced gut damage and weight loss [3,4,5,6,7]. The additional growth factors and nutrients not only provide excess energy sources for GI epithelium, which assists in protecting these cells against catabolic conditions, but also have more specific biological actions intended to ameliorate tissue damage associated with mucositis [8,9].…”

Section: Introductionmentioning

confidence: 99%

“…Studies investigating Clinutren Protect ® [4,5], Modulen ® [6], TGF-β [3,7], and l -glutamine [11,17,18] for prevention of methotrexate-induced gut damage have been previously undertaken with success. However, it is known that tumor burden is associated with significantly increased chemotherapy-induced gut toxicity [19].…”

Section: Introductionmentioning

confidence: 99%

Investigation of Effect of Nutritional Drink on Chemotherapy-Induced Mucosal Injury and Tumor Growth in an Established Animal Model

et al. 2013

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Chemotherapy-induced mucositis represents a significant burden to quality of life and healthcare costs, and may be improved through enhanced nutritional status. We first determined the safety of two nutritional drinks (plus placebo), and then potential gut protection in tumor-bearing rats in a model of methotrexate-induced mucositis. In study 1, animals were fed one of two test diets (or placebo or control chow pellets) for a total of 60 days and were monitored daily. All diets were found to be safe to administer. In study 2, after seven days of receiving diets, a Dark Agouti Mammary Adenocarcinoma (DAMA) was transplanted subcutaneously. Ten days after starting diets, animals had 2 mg/kg intramuscular methotrexate administered on two consecutive days; after this time, all animals were given soaked chow. Animals were monitored daily for changes in bodyweight, tumor burden and general health. Animals were killed 10, 12 and 16 days after initially starting diets, and tissues were collected at necropsy. In study 1, animals receiving diets had gained 0.8% and 10.8% of their starting bodyweight after 60 days, placebo animals 4.4%, and animals fed on standard chow had gained 15.1%. In study 2, there was no significant influence of test diet on bodyweight, organ weight, tumor burden or biochemical parameters. Only animals treated with MTX exhibited diarrhea, although animals receiving Diet A and Diet C showed a non-significant increase in incidence of diarrhea. Administration of these nutritional drinks did not improve symptoms of mucositis.

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A Diet Containing Whey Protein, Glutamine, and TGFβ Modulates Gut Protein Metabolism During Chemotherapy-Induced Mucositis in Rats

Abstract: Clinutren Protect feeding reduces intestinal injury in the acute phase of methotrexate-induced mucositis in rats and improves recovery.

Cited by 17 publications

References 33 publications

Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model

Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model

A regular curd consumption improves gastrointestinal status assessed by a randomized controlled nutritional intervention

Investigation of Effect of Nutritional Drink on Chemotherapy-Induced Mucosal Injury and Tumor Growth in an Established Animal Model

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