Effect of oral glutamine on enterocyte turnover during methotrexate-induced mucositis in rats.
OBJECTIVE
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.
Sukhotnik
Igor
I
Rappaport Faculty of Medicine, Technion, Laboratory of Intestinal Adaptation and Recovery, Bnai Zion Medical Center, Haifa, Israel. igor-dr@internet-zahav.net
Mogilner
Jorge G
JG
Karry
Rahel
R
Shamian
Benhoor
B
Lurie
Michael
M
Kokhanovsky
Natalie
N
Ure
Benno M
BM
Coran
Arnold G
AG
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020895:Enterocytes / Q000187:drug effects* / Q000378:metabolism; D005973:Glutamine / Q000008:administration & dosage / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008727:Methotrexate; D052016:Mucositis / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D005973:Glutamine; D008727:Methotrexate