title: Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Treatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat.
authors.affiliation: The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Laboratory of intestinal adaptation and recovery, Haifa, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Koppelmann
authors.forename: Yulia
authors.initials: Y
authors.lastname: Pollak
authors.forename: Jorge
authors.initials: J
authors.lastname: Mogilner
authors.forename: Jacob
authors.initials: J
authors.lastname: Bejar
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Coran
authors.forename: Igor
authors.initials: I
authors.lastname: Sukhotnik
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D019587:Dietary Supplements; D020895:Enterocytes / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D019254:Genes, bcl-2; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007583:Jejunum / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D001120:Arginine; D008727:Methotrexate