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

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Abstract

Background

Mucositis, a common side effect of chemotherapy, is characterized by compromised digestive function, barrier integrity and immune competence.

Aims

Our aim was to evaluate the impact of a specifically designed diet Clinutren Protect® (CP), which contains whey proteins, TGFβ-rich casein, and free glutamine, on mucositis in rats.

Methods

Mucositis was induced by three consecutive injections (day 0, day 1, day 2) of methotrexate (2.5 mg/kg). Rats had free access to CP or placebo diets from days −7 to 9. In the placebo diet, whey proteins and TGFβ-rich casein were replaced by TGFβ-free casein and glutamine by alanine. Intestinal parameters were assessed at day 3 and 9. Values, expressed as mean ± SEM, were compared using two-way ANOVA.

Results

At day 3, villus height was markedly decreased in the placebo (296 ± 11 μm) and CP groups (360 ± 10 μm) compared with controls (464 ± 27 μm), but more markedly in the placebo as compared to CP group. The intestinal damage score was also reduced in the CP compared with the placebo group. Glutathione content increased in the CP compared with the placebo group (2.2 ± 0.2 vs. 1.7 ± 0.2 μmol/g tissue). Gut protein metabolism was more affected in the placebo than in the CP group. The fractional synthesis rate was decreased in the placebo group (93.8 ± 4.9%/day) compared with controls (121.5 ± 12.1, P < 0.05), but not in the CP group (106.0 ± 13.1). In addition, at day 9, rats exhibited improved body weight and food intake recovery in the CP compared to the placebo group.

Conclusions

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

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Abbreviations

BCAA:

branched chain amino acids

CP:

Clinutren Protect®

FSR:

fractional synthesis rate

GSH:

glutathione

IL:

interleukin

MTX:

methotrexate

PGPH:

peptidyl glutamyl peptide hydrolysis

TGFβ:

transforming growth factor β

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Acknowledgments

The skillful technical assistance of Brigitte Maurer (Laboratory of Medical Biochemistry, Rouen University Hospital) is gratefully acknowledged. We also thank Dr Richard Medeiros (Medical Editor, Rouen University Hospital) for his advice in editing the manuscript.

Conflict of Interest

PD received honoraries for lectures by Nestlé Nutrition. MF, JV and DB are employees of Nestlé. None of the other authors had a conflict of interest to disclose.

Author information

Authors and Affiliations

  1. ADEN EA4311 Institute for Biomedical Research and European Institute for Peptide Research (IFRMP23), Rouen University, 22 boulevard Gambetta, 76183, Rouen cedex 1, France

    Nabile Boukhettala, Ayman Ibrahim, Sophie Claeyssens, Alain Lavoinne, Pierre Déchelotte & Moïse Coëffier

  2. Laboratory of Medical Biochemistry, Rouen University Hospital, Rouen, France

    Sophie Claeyssens & Alain Lavoinne

  3. Nutrition and Health Department, Nestlé Research Center, Lausanne, Switzerland

    Magali Faure, Jacques Vuichoud & Denis Breuillé

  4. Laboratory of Anatomo-Pathology, Rouen University Hospital, Rouen, France

    Florence Le Pessot

  5. Nutrition Unit, Rouen University Hospital, Rouen, France

    Pierre Déchelotte & Moïse Coëffier

Authors
  1. Nabile Boukhettala
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  2. Ayman Ibrahim
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  3. Sophie Claeyssens
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  4. Magali Faure
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  5. Florence Le Pessot
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  6. Jacques Vuichoud
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  7. Alain Lavoinne
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  8. Denis Breuillé
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  9. Pierre Déchelotte
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  10. Moïse Coëffier
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Corresponding author

Correspondence to Moïse Coëffier.

Additional information

The study was supported by Nestlé Research Center, Nutrition and Health Department, Lausanne, Switzerland.

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Boukhettala, N., Ibrahim, A., Claeyssens, S. et al. A Diet Containing Whey Protein, Glutamine, and TGFβ Modulates Gut Protein Metabolism During Chemotherapy-Induced Mucositis in Rats. Dig Dis Sci 55, 2172–2181 (2010). https://doi.org/10.1007/s10620-009-1039-2

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  • DOI: https://doi.org/10.1007/s10620-009-1039-2

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