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Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat

Tal Koppelmann13, Yulia Pollak1, Jorge Mogilner2, Jacob Bejar4, Arnold G Coran5 and Igor Sukhotnik12*

Author Affiliations

1 The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Laboratory of intestinal adaptation and recovery, Haifa, Israel

2 Department of Pediatric Surgery, Bnai Zion Medical Center, Haifa, Israel

3 Department of Surgery, Bnai Zion Medical Center, Haifa, Israel

4 Department of Pathology, Bnai Zion Medical Center, Haifa, Israel

5 Section of Pediatric Surgery C.S. Mott Children's Hospital and University of Michigan Medical School, Ann Arbor, MI, USA

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BMC Gastroenterology 2012, 12:41  doi:10.1186/1471-230X-12-41

Published: 30 April 2012



Arginine (ARG) and nitric oxide maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluated the effects of oral ARG supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat.


Male rats were divided into four experimental groups: Control rats, CONTR-ARG rats, were treated with oral ARG given in drinking water 72 hours before and 72 hours following vehicle injection, MTX rats were treated with a single dose of methotrexate, and MTX-ARG rats were treated with oral ARG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. RT-PCR was used to determine bax and bcl-2 mRNA expression.


MTX-ARG rats demonstrated greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-ARG rats (vs MTX) was accompanied by decreased bax mRNA and protein expression and increased bcl-2 protein levels.


Treatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat.

Methotrexate; Mucositis; Intestine; Arginine; Rat