Effects of topical application of methotrexate on nasal mucosa in rats:: A preclinical assessment study

Objective: The aim of this study is to investigate dose-dependent effect of the topical application of methotrexate (MTX) in rats on the normal nasal mucosa, liver tissue, liver enzymes, and hemoglobin levels. Study Design: Preclinical animal study. Setting: Twenty male adult wistar albino rats were randomly divided into 4 groups (n=5). A single puff of MTX (2.5 mu g) was applied to both nasal cavities 2 times a day. The animals were given MTX I day a week in group 1, 3 days a week in group 2, and 5 days a week in group 3. Control group animals were given I puff of physiologic saline to both nasal cavities 5 days a week and 2 times a day. After 28 days, liver biopsies, blood samples, and 5 nasal mucosal biopsies were taken. Histological examination was made with respect to certain parameters semiquantitatively (grade 0-3). The aspartate aminotransferase (AST) and alanine amino-transferase (ALT) levels and hemoglobin counts were studied from blood samples. Results: There are no statistically significant differences with respect to histopathological parameters between the control group and the groups 1-3 (P>0.05). Histopathological examination of liver tissue did not reveal any evident difference between the control and study groups. Mean AST and ALT as liver function tests and hemoglobin Counts were within normal limits. Topical application of MTX at these doses hits no toxic effect on the nasal mucosa, the liver tissue, AST and ALT levels, and hemoglobin level. Conclusions: These results have been encouraging to investigate use of the topical application of MTX in nasal manifestation of autoimmune disease or addition of the topical application of MTX to the steroid treatment in cases with massive nasal polyposis resistant to steroids and prone to recurrence. 2006 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved.