Alanyl-glutamine hastens morphologic recovery from 5-fluorouracil-induced mucositis in mice

Nutrition. 2004 Oct;20(10):934-41. doi: 10.1016/j.nut.2004.06.016.

Abstract

Objective: In this study, we postulated the beneficial role of oral alanyl-glutamine, a more stable glutamine derivative to decrease 5-fluorouracil (5-FU)-induced mucositis in mice.

Methods: We measured different morphologic parameters to assess structural changes over time in the small bowel, including crypt depth, villus height, villus area, mitotic and apoptotic indices at the crypt level using terminal deoxyuridine triphosphate nick end labeling, and hematoxylin-eosin staining of ileal tissue. In addition, we analyzed the effect of different alanyl-glutamine concentrations on animal weight curves after 5-FU treatment.

Results: Neither glutamine nor alanyl- glutamine prevented the 5-FU intestinal structural damage or apoptosis in crypt enterocytes at 24 h after 5-FU challenge. However, we found that alanyl-glutamine, but not glutamine, speeds intestinal recovery when compared with 5-FU-treated controls (P < 0.05), predominantly by enhancing mitotic activity and crypt length.

Conclusion: Our findings provide important data to support clinical studies of oral alanyl-glutamine in 5-FU-induced mucositis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / toxicity
  • Apoptosis / drug effects
  • Body Weight / drug effects
  • Cell Division / drug effects
  • Dipeptides / administration & dosage*
  • Dose-Response Relationship, Drug
  • Fluorouracil / toxicity
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C

Substances

  • Antimetabolites, Antineoplastic
  • Dipeptides
  • Fluorouracil
  • alanylglutamine