title: Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease.
abstract: BACKGROUND
  Reactive oxygen species contribute to tissue injury in inflammatory bowel disease (IBD). The tripeptide glutathione (GSH) is the most important intracellular antioxidant.
  
  
  OBJECTIVE
  To investigate constituent amino acid plasma levels and the GSH redox status in different compartments in IBD with emphasis on intestinal GSH synthesis in Crohn's disease.
  
  
  METHODS
  Precursor amino acid levels were analysed in plasma and intestinal mucosa. Reduced (rGSH) and oxidised glutathione (GSSG) were determined enzymatically in peripheral blood mononuclear cells (PBMC), red blood cells (RBC), muscle, and in non-inflamed and inflamed ileum mucosa. Mucosal enzyme activity of gamma-glutamylcysteine synthetase (gamma GCS) and gamma-glutamyl transferase (gamma GT) was analysed. Blood of healthy subjects and normal mucosa from a bowel segment resected for tumor growth were used as controls.
  
  
  RESULTS
  Abnormally low plasma cysteine and cystine levels were associated with inflammation in IBD (p < 10(-4)). Decreased rGSH levels were demonstrated in non-inflamed mucosa (p < 0.01) and inflamed mucosa (p = 10(-6)) in patients with IBD, while GSSG increased with inflammation (p = 0.007) compared with controls. Enzyme activity of gamma GCS was reduced in non-inflamed mucosa (p < 0.01) and, along with gamma GT, in inflamed mucosa (p < 10(-4)). The GSH content was unchanged in PBMC, RBC, and muscle.
  
  
  CONCLUSIONS
  Decreased activity of key enzymes involved in GSH synthesis accompanied by a decreased availability of cyst(e)ine for GSH synthesis contribute to mucosal GSH deficiency in IBD. As the impaired mucosal antioxidative capacity may further promote oxidative damage, GSH deficiency might be a target for therapeutic intervention in IBD.
authors.affiliation: Department of Surgery, University of Heidelberg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Sido
authors.forename: V
authors.initials: V
authors.lastname: Hack
authors.forename: A
authors.initials: A
authors.lastname: Hochlehnert
authors.forename: H
authors.initials: H
authors.lastname: Lipps
authors.forename: C
authors.initials: C
authors.lastname: Herfarth
authors.forename: W
authors.initials: W
authors.lastname: Dröge
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000097:blood; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism; D010084:Oxidation-Reduction; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D000596:Amino Acids; D005723:gamma-Glutamyltransferase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione