Alanyl-glutamine 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.


CONCLUSIONS
Our findings provide important data to support clinical studies of oral alanyl-glutamine in 5-FU-induced mucositis.
Department of Morphology, Institute of Biomedicine and Clinical Research Unit-University Hospital, Federal University of Ceará, Brazil.
Benedito A
BA
Carneiro-Filho
Reinaldo B
RB
Oriá
Katie
K
Wood Rea
Gerly A C
GA
Brito
Jun
J
Fujii
Tom
T
Obrig
Aldo A M
AA
Lima
Richard L
RL
Guerrant
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004151:Dipeptides / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000633:toxicity; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D000964:Antimetabolites, Antineoplastic; D004151:Dipeptides; D005472:Fluorouracil; C054122:alanylglutamine