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Glutathione is required for intestinal function.

J Mårtensson1, A Jain, A Meister

  • 1Department of Biochemistry, Cornell University Medical College, New York, NY 10021.

Proceedings of the National Academy of Sciences of the United States of America
|March 1, 1990
PubMed
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Glutathione (GSH) deficiency damages the gut lining, but oral GSH or GSH esters can prevent this. GSH is not easily transported from blood to tissues, suggesting alternative uptake mechanisms for gut protection.

Area of Science:

  • Biochemistry
  • Gastroenterology
  • Cell Biology

Background:

  • Glutathione (GSH) is a critical antioxidant. GSH deficiency, induced by buthionine sulfoximine in mice, causes severe jejunum and colon epithelial cell damage.
  • Previous studies suggest limited transport of intact GSH from plasma to various tissues, including the lens, lung, and liver.

Purpose of the Study:

  • To investigate the protective effects of GSH and its esters against GSH deficiency-induced intestinal damage in mice.
  • To explore the mechanisms of GSH uptake and utilization by gastrointestinal epithelial cells.

Main Methods:

  • Induction of GSH deficiency using buthionine sulfoximine in mice.
  • Administration of oral or intraperitoneal GSH monoester and oral or intraperitoneal GSH.
  • Measurement of GSH levels in plasma, intestinal mucosa, and pancreas.

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Main Results:

  • GSH deficiency led to significant degeneration of jejunum and colon epithelial cells.
  • Oral GSH monoester and oral GSH prevented this degeneration.
  • Intraperitoneal GSH administration increased plasma GSH but not intestinal GSH levels.
  • Extracellular GSH appears to be utilized via cleavage, uptake of products, and intracellular synthesis.

Conclusions:

  • Oral administration of GSH or its esters is effective in protecting the gastrointestinal epithelium from GSH deficiency.
  • Gastrointestinal cells may utilize extracellular GSH through specific uptake mechanisms, including lumenal uptake.
  • Biliary GSH likely plays a role in protecting the intestinal mucosa, and GSH administration may support cysteine synthesis for cellular GSH production.