Effect of oral glutamine on enterocyte turnover during methotrexate-induced mucositis in rats

Igor Sukhotnik, Jorge G Mogilner, Rahel Karry, Benhoor Shamian, Michael Lurie, Natalie Kokhanovsky, Benno M Ure, Arnold G Coran
Digestion 2009, 79 (1): 5-13

BACKGROUND/AIMS: The objective of this study was to evaluate the effects of oral glutamine in preventing intestinal mucosal damage caused by methotrexate (MTX) in rats.

METHODS: Male Sprague-Dawley rats were divided into 3 experimental groups: control rats, rats treated intraperitoneally with MTX (MTX rats) and rats treated with oral glutamine in the drinking water (2%) 72 h following intraperitoneal injection of a single dose of MTX (MTX-glutamine rats). Intestinal mucosal damage (Park's injury score), mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 h following MTX injection. RT-PCR was used to determine Bax and Bcl-2 mRNA expression.

RESULTS: MTX-glutamine rats demonstrated greater jejunal and ileal mucosal weight and mucosal DNA, greater ileal villus height and crypt depth, and a greater index of proliferation in the jejunum and ileum compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-glutamine rats (vs. MTX) was accompanied by decreased Bax and increased Bcl-2 mRNA expression.

CONCLUSIONS: Treatment with oral glutamine prevents mucosal injury and improves intestinal recovery following MTX injury in the rat.

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