| Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease. | |
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MedLine Citation:
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PMID: 9616308 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Reactive oxygen species contribute to tissue injury in inflammatory bowel disease (IBD). The tripeptide glutathione (GSH) is the most important intracellular antioxidant. AIMS: 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. |
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Authors:
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B Sido; V Hack; A Hochlehnert; H Lipps; C Herfarth; W Dröge |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Gut Volume: 42 ISSN: 0017-5749 ISO Abbreviation: Gut Publication Date: 1998 Apr |
Date Detail:
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Created Date: 1998-06-16 Completed Date: 1998-06-16 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 2985108R Medline TA: Gut Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 485-92 Citation Subset: AIM; IM |
Affiliation:
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Department of Surgery, University of Heidelberg, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Amino Acids / blood Colitis, Ulcerative / metabolism* Crohn Disease / metabolism* Erythrocytes / metabolism Female Glutamate-Cysteine Ligase / metabolism Glutathione / biosynthesis*, metabolism Humans Intestinal Mucosa / metabolism* Leukocytes, Mononuclear / metabolism Male Middle Aged Muscle, Skeletal / metabolism Oxidation-Reduction gamma-Glutamyltransferase / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 70-18-8/Glutathione; EC 2.3.2.2/gamma-Glutamyltransferase; EC 6.3.2.2/Glutamate-Cysteine Ligase |
| Comments/Corrections | |
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