Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats

Abstract

Context - Methotrexate and other anticancer agents can induce intestinal mucositis, which is one of the most common limiting factor that prevent further dose escalation of the methotrexate. Objectives - To evaluate the gastric emptying and gastrointestinal transit of liquids in methotrexate-induced intestinal mucositis. Methods - Wistar rats received methotrexate (2.5 mg/kg/day for 3 days, subcutaneously) or saline. After 1, 3 and 7 days, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage and myeloperoxidase activity (biochemical marker of granulocyte infiltration). Others rats were pre-treated with methotrexate or saline, gavage-fed after 3 or 7 days with a standard test liquid meal, and sacrificed 10, 20 or 30-min later. Gastric and small intestine dye recoveries were measured by spectrophotometry. Results - After 3 days of methotrexate, there was an epithelial intestinal damage in all segments, with myeloperoxidase activity increase in both in duodenum and ileum. Seven days after methotrexate, we observed a complete reversion of this intestinal damage. There was an increase in gastric dye recoveries after 10, 20, and 30-min post-prandial intervals after 3 days, but not after 7 days, of methotrexate. Intestine dye recoveries were decreased in the first and second segments at 10 min, in the third at 20 min, and in the second and third at 30 min, only after 3 days of methotrexate treatment. Conclusion - Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats.