title: Glutamine prevents intestinal mucosal injury induced by cyclophosphamide in rats.
abstract: OBJECTIVE
  High doses of anticancer drugs often damage the intestinal mucosa. The purpose of the present study was to examine the effect of glutamine on mucosal damage induced by cyclophosphamide in a rat model, and to elucidate the mechanisms responsible for its protective effects.
  
  
  METHODS
  Rats were randomly assigned to one of the three experimental groups. Group A (control) (n = 8): intraperitoneal injection of saline, group B (n = 8): intraperitoneal injection of cyclophosphamide (300 mg/kg), group C (n = 8): intraperitoneal injection of cyclophosphamide (300 mg/kg) and oral glutamine (1.0 g/kg). After 3 days, the ileal segment was removed for morphological and the biochemical analyses. We also evaluated the level of mucosal apoptosis by the TUNEL method and enterocyte proliferation using bromodeoxyuridine (BrdU).
  
  
  RESULTS
  Mucosal atrophy was observed in group B but not in groups A or C. The mucosal wet weight, protein and glutathione levels were significantly decreased in group B compared with group A, and were increased significantly in group C compared with group B. While enterocyte proliferation significantly decreased and the apoptotic index significantly increased in group B compared with group A, a significant increase in the enterocyte proliferation and a significant decrease in apoptosis were observed in group C compared with group B.
  
  
  CONCLUSIONS
  Glutamine prevented intestinal mucosal injury induced by cyclophosphamide via increased glutathione, decreased apoptosis and increased proliferation of intestinal epithelial cells.
authors.affiliation: Department of Surgery, Division of Pediatric Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Owari
authors.forename: Masafumi
authors.initials: M
authors.lastname: Wasa
authors.forename: Takaharu
authors.initials: T
authors.lastname: Oue
authors.forename: Satoko
authors.initials: S
authors.lastname: Nose
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuzawa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003520:Cyclophosphamide / Q000633:toxicity; D004195:Disease Models, Animal; D020895:Enterocytes / Q000187:drug effects / Q000473:pathology*; D005973:Glutamine / Q000008:administration & dosage*; D007077:Ileal Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007082:Ileum / Q000187:drug effects* / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D005973:Glutamine; D003520:Cyclophosphamide