IMPAIRMENT OF INTESTINAL GLUTATHIONE SYNTHESIS IN PATIENTS WITH INFLAMMATORY BOWEL-DISEASE

Background-Reactive oxygen species contribute to tissue injury in infl ammatory bowel disease (IBD). The tripeptide glutathione (GSH) is the most important intracellular antioxidant. Aims-To investigate constitu ent amino acid plasma levels and the GSH redox status in different com partments in IBD with emphasis on intestinal GSH synthesis in Crohn's disease. Methods-Precursor amino acid levels were analysed in plasma a nd intestinal mucosa. Reduced (rGSH) and oxidised glutathione (GSSG) w ere determined enzymatically in peripheral blood mononuclear cells (PB MC), red blood cells (RBC), muscle, and in non-inflamed and inflamed i leum mucosa. Mucosal enzyme activity of gamma-glutamylcysteine synthet ase (gamma GCS) and gamma-glutamyl transferase (gamma GT) was analysed . Blood of healthy subjects and normal mucosa from a bowel segment res ected for tumour growth were used as controls. Results-Abnormally low plasma cysteine and cystine levels were associated with inflammation i n IBD (p<10(-4)). Decreased rGSH levels were demonstrated in noninflam ed mucosa (p<0.01) and inflamed mucosa (p=10(-6)) in patients with IBD , while GSSG increased with inflammation (p=0.007) compared with contr ols. 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 G SH content was unchanged in PBMC, RBC, and muscle. Conclusions-Decreas ed activity of key enzymes involved in GSH synthesis accompanied by a decreased availability of cyst(e)ine for GSH synthesis contribute to m ucosal GSH deficiency in IBD. As the impaired mucosal antioxidative ca pacity may further promote oxidative damage, GSH deficiency might be a target for therapeutic intervention in IBD.