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

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. (C)Elsevier Inc. 2004.