Dual Beneficial Effects of Topical <scp>l</scp> ‐Glutamine on Oral Mucositis in 5‐Fluorouracil‐Treated Mice

BACKGROUND: Oral mucositis is a severe health and economic problem that occurs in about 40%-90% of patients undergoing cancer treatments. Systemic or topical application of l-glutamine has been shown to improve mucosal healing and ameliorate oral mucositis (OM) symptoms according to clinical score systems. To further establish the beneficial effects of this amino acid, our study examined the actions of topical application of l-glutamine on inflammation and mucosal healing markers in tongue lesions in mice treated with 5-Fluorouracil. METHODS: The animals received 3 doses of the chemotherapeutic agent (non-consecutive days) at concentrations of 60, 40, and 40 mg/kg, respectively. Tongue lesions were made by acetic acid (bolus injection) on the ventral face. Ten mg/50 μL of l-glutamine were applied at the site of the lesion in the treated group (n = 15) twice a day for 5 days; the control group (n = 15) received filtered water. On day 6, the animals were euthanized, the tongues removed, and processed for inflammatory and fibrogenic markers. RESULTS: The treatment decreased myeloperoxidase (MPO) and N-acetyl-β-glucosaminidase (NAG) activities, tumor necrosis factor alpha levels (TNF-α), and mast cell numbers at the site of the lesions. The amino acid was able to decrease the number of Ki-67 positive cells in the treated group. There was increased mucosal remodeling through collagen deposition in the treated group. CONCLUSION: Topical application of l-glutamine acted on multiple axes of OM, modulating inflammation and tissue remodeling in immunosuppressed mice.