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Updated: Jun 26, 2026

Ex Vivo Intestinal Sacs to Assess Mucosal Permeability in Models of Gastrointestinal Disease
Published on: February 9, 2016
Effect of oral glutamine on enterocyte turnover during methotrexate-induced mucositis in rats
Igor Sukhotnik1, Jorge G Mogilner, Rahel Karry
1Rappaport Faculty of Medicine, Technion, Laboratory of Intestinal Adaptation and Recovery, Bnai Zion Medical Center, Haifa, Israel. igor-dr@internet-zahav.net
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.
Insights
Oral glutamine supplementation effectively prevents intestinal damage caused by methotrexate (MTX) chemotherapy in rats. This study shows glutamine improves gut mucosal recovery and reduces cell death after MTX treatment.
Area of Science:
- Gastroenterology
- Pharmacology
- Cell Biology
Background:
- Methotrexate (MTX) chemotherapy can cause significant intestinal mucosal damage.
- Protecting the gut lining during MTX treatment is crucial for patient well-being.
- Oral glutamine is investigated as a potential therapeutic agent to mitigate MTX-induced enteropathy.
Purpose of the Study:
- To assess the efficacy of oral glutamine in preventing methotrexate-induced intestinal mucosal injury in a rat model.
- To evaluate the impact of glutamine on structural and cellular recovery of the intestine post-MTX exposure.
Main Methods:
- Male Sprague-Dawley rats were assigned to control, MTX-only, or MTX plus oral glutamine groups.
- Intestinal mucosal damage, structural integrity, enterocyte proliferation, and apoptosis were assessed 72 hours after MTX administration.
- Gene expression of apoptosis markers (Bax and Bcl-2) was analyzed using RT-PCR.
Main Results:
- Glutamine treatment preserved jejunal and ileal mucosal weight and DNA content compared to MTX-only rats.
- Oral glutamine enhanced ileal villus height, crypt depth, and enterocyte proliferation in both jejunum and ileum.
- A significant reduction in ileal enterocyte apoptosis was observed in glutamine-treated rats, associated with altered Bax and Bcl-2 mRNA levels.
Conclusions:
- Oral glutamine administration effectively prevents intestinal mucosal injury induced by methotrexate in rats.
- Glutamine supplementation promotes intestinal recovery and improves mucosal integrity following MTX chemotherapy.
- These findings suggest glutamine as a potential supportive therapy for MTX-treated patients to reduce gastrointestinal side effects.
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