Glutathione is required for intestinal function.
Glutathione (GSH) deficiency produced in mice by giving buthionine sulfoximine leads to severe degeneration of the epithelial cells of the jejunum and colon. This is prevented by giving GSH monoester (orally or i.p.) and also by giving GSH (orally, but not i.p.). The i.p. administration leads to high plasma levels of GSH but does not appreciably increase GSH levels in intestinal mucosa or pancreas. These and previous studies on lens, lung, lymphocytes, liver, heart, and skeletal muscle indicate that there is very little, if any, transport of intact GSH from plasma to these tissues. Cells can use extracellular GSH by a pathway involving its cleavage, uptake of products and intracellular GSH synthesis. Epithelial cells of the gastrointestinal tract may use this pathway and can also take up lumenal GSH (which arises partly from the bile) by a mechanism(s) that may involve transport of dipeptides or of GSH. It is suggested that biliary GSH normally functions in the protection of intestinal mucosa. Administration of GSH may be protective of the gastrointestinal epithelium and may also serve as a good source of cysteine moieties for intracellular GSH synthesis in the gastrointestinal tract and in other tissues. Administration of GSH delivery agents such as GSH esters is more effective than administration of GSH in increasing cellular and mitochondrial levels of GSH.
Mårtensson
J
J
Department of Biochemistry, Cornell University Medical College, New York, NY 10021.
Jain
A
A
Meister
A
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019328:Buthionine Sulfoximine; D004848:Epithelium / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D005978:Glutathione / Q000031:analogs & derivatives* / Q000172:deficiency / Q000378:metabolism* / Q000633:toxicity; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D007583:Jejunum / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000633:toxicity; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D012016:Reference Values
D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; C058293:glutathione monoisopropyl ester; D005978:Glutathione