GUT 1998;42:485-492 ( April )

Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease

B Sido,^a V Hack,^b A Hochlehnert,^a H Lipps,^b C Herfarth,^a W Dröge^b

^a Department of Surgery, University of Heidelberg, Heidelberg, Germany, ^b Department of Immunochemistry, German Cancer Research Center, Heidelberg, Germany

Correspondence to: Dr B Sido, Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.

Accepted for publication 31 October 1997

BackgroundReactive oxygen species contribute to tissue injury in inflammatory bowel disease (IBD). The tripeptide glutathione (GSH) is the most important intracellular antioxidant.
AimsTo 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.
MethodsPrecursor 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 -glutamylcysteine synthetase (GCS) and -glutamyl transferase (GT) was analysed. Blood of healthy subjects and normal mucosa from a bowel segment resected for tumour growth were used as controls.
ResultsAbnormally 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 GCS was reduced in non-inflamed mucosa (p<0.01) and, along with GT, in inflamed mucosa (p<10^-4). The GSH content was unchanged in PBMC, RBC, and muscle.
ConclusionsDecreased 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.
(GUT 1998;42:485-492)

Keywords: Crohn's disease;  ulcerative colitis;  glutathione;  amino acids;  -glutamylcysteine synthetase;  mucosa

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© 1998 by Gut
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