Digestive Diseases and Sciences

, Volume 55, Issue 8, pp 2172–2181

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

  • Nabile Boukhettala
  • Ayman Ibrahim
  • Sophie Claeyssens
  • Magali Faure
  • Florence Le Pessot
  • Jacques Vuichoud
  • Alain Lavoinne
  • Denis Breuillé
  • Pierre Déchelotte
  • Moïse Coëffier
Original Article

DOI: 10.1007/s10620-009-1039-2

Cite this article as:
Boukhettala, N., Ibrahim, A., Claeyssens, S. et al. Dig Dis Sci (2010) 55: 2172. doi:10.1007/s10620-009-1039-2

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.

Keywords

ChemotherapyNutritionMucositisGlutamineWhey proteinsTGFβ

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

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Nabile Boukhettala
    • 1
  • Ayman Ibrahim
    • 1
  • Sophie Claeyssens
    • 1
    • 2
  • Magali Faure
    • 3
  • Florence Le Pessot
    • 4
  • Jacques Vuichoud
    • 3
  • Alain Lavoinne
    • 1
    • 2
  • Denis Breuillé
    • 3
  • Pierre Déchelotte
    • 1
    • 5
  • Moïse Coëffier
    • 1
    • 5
  1. 1.ADEN EA4311 Institute for Biomedical Research and European Institute for Peptide Research (IFRMP23)Rouen UniversityRouen cedex 1France
  2. 2.Laboratory of Medical BiochemistryRouen University HospitalRouenFrance
  3. 3.Nutrition and Health DepartmentNestlé Research CenterLausanneSwitzerland
  4. 4.Laboratory of Anatomo-PathologyRouen University HospitalRouenFrance
  5. 5.Nutrition UnitRouen University HospitalRouenFrance