Glutamine and alanyl-glutamine accelerate the recovery from 5-fluorouracil-induced experimental oral mucositis in hamster.
BACKGROUND
Mucositis induced by anti-neoplastic drugs is an important, dose-limiting and costly side effect of cancer therapy.


OBJECTIVE
To evaluate the effect of oral glutamine and alanyl-glutamine, a more stable glutamine derivative, on 5-FU-induced oral mucositis in hamsters.


METHODS
Oral mucositis was induced by two intraperitoneal (i.p) administrations of 5-FU on the first and second days of the experiment (60 and 40 mg/kg, respectively) followed by mechanical trauma on the fourth day in male hamsters. Animals received saline, glutamine or alanyl-glutamine suspension (100 mM) 1 h before the injections of 5-FU and daily until sacrifice, on the 10th or 14th day. Macroscopic and histopathological analyses were evaluated and graded. Tissues from the cheek pouches were harvested for measurement of myeloperoxidase activity and glutathione stores. For investigation of serum concentration of glutamine, blood was obtained by heart puncture from anesthetized animals before sacrifice, on day 10.


RESULTS
Treatment with glutamine and alanyl-glutamine reduced macroscopic and histological parameters of oral mucositis, and reduced the myeloperoxidase activity on day 14, but not on day 10. The 5-FU-induced oral mucositis significantly decreased the serum glutamine levels as well as the cheek pouch glutathione stores observed on day 10. Glutamine or alanyl-glutamine administration reversed the 5-FU effects, restoring serum glutamine levels and cheek pouch glutathione stores, observed on day 10, but did not prevent oral mucositis on the tenth day.


CONCLUSIONS
Glutamine or alanyl-glutamine accelerated the mucosal recovery increasing mucosal tissue glutathione stores, reducing inflammatory parameters and speeding reepithelization.
Leitão
R F C
RF
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil.
Ribeiro
R A
RA
Lira
A M S
AM
Silva
L R
LR
Bellaguarda
E A L
EA
Macedo
F D B
FD
Sousa
R B
RB
Brito
G A C
GA
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D006224:Cricetinae; D004151:Dipeptides / Q000627:therapeutic use*; D005472:Fluorouracil / Q000633:toxicity*; D005973:Glutamine / Q000097:blood / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D013280:Stomatitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D004151:Dipeptides; D013438:Sulfhydryl Compounds; D005973:Glutamine; D009195:Peroxidase; D005978:Glutathione; D005472:Fluorouracil; C054122:alanylglutamine