Glutamine and alanyl-glutamine accelerate the recovery from 5-fluorouracil-induced experimental oral mucositis in hamster

• Published in: Cancer chemotherapy and pharmacology Vol. 61; no. 2; pp. 215 - 222
• Main Authors: Leitão, R. F. C., Ribeiro, R. A., Lira, A. M. S., Silva, L. R., Bellaguarda, E. A. L., Macedo, F. D. B., Sousa, R. B., Brito, G. A. C.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-02-2008; Springer; Springer Nature B.V
• Subjects: Animals; Antimetabolites, Antineoplastic - toxicity; Antineoplastic agents; Biological and medical sciences; Cancer Research; Cricetinae; Dipeptides - therapeutic use; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Fluorouracil - toxicity; Glutamine - blood; Glutamine - therapeutic use; Glutathione - metabolism; Male; Medical sciences; Medicine; Medicine & Public Health; Mesocricetus; Mouth Mucosa - pathology; Neutrophil Infiltration - drug effects; Non tumoral diseases; Oncology; Original Article; Otorhinolaryngology. Stomatology; Peroxidase - metabolism; Pharmacology. Drug treatments; Pharmacology/Toxicology; Stomatitis - chemically induced; Stomatitis - drug therapy; Stomatitis - pathology; Sulfhydryl Compounds - metabolism; 5-fluorouracil; Oral mucositis; Alanyl-glutamine; Glutamine; Antineoplastic agent; Enzyme; Stomatology; Fluoropyrimidine derivatives; Transferases; Rodentia; Enzyme inhibitor; Thymidylate synthase; Recovery; Vertebrata; Stomatitis; Mammalia; Antimetabolic; Methyltransferases; Aminoacid; Animal; Pyrimidine derivatives; Oral cavity disease; Hamster; Fluorouracil
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-007-0463-2

Introduction
Mucositis induced by anti-neoplastic drugs is an important, dose-limiting and costly side effect of cancer therapy.
Aim
To evaluate the effect of oral glutamine and alanyl-glutamine, a more stable glutamine derivative, on 5-FU-induced oral mucositis in hamsters.
Materials and 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.
Conclusion
Glutamine or alanyl-glutamine accelerated the mucosal recovery increasing mucosal tissue glutathione stores, reducing inflammatory parameters and speeding reepithelization.