In vitro and ex vivo uptake of glutathione (GSH) across the intestinal epithelium and fate of oral GSH after in vivo supplementation

J Agric Food Chem. 2014 Oct 1;62(39):9499-506. doi: 10.1021/jf503257w. Epub 2014 Sep 22.


Glutathione (GSH) is the most prevalent low-molecular-weight thiol in mammalian cells and is crucial for antioxidant defense, nutrient metabolism, and the regulation of pathways essential for whole body homeostasis. GSH transport systems have been identified in the membranes of various tissues and organs, including the small intestine. However, little is known regarding GSH transport across intestinal epithelial cells. The current in vitro and ex vivo uptake study of GSH demonstrated that intact GSH can be transported across intestinal epithelial cells, suggesting that GSH uptake is not proton-dependent. It would appear that the initial uptake of GSH into cells is a rapid process. Furthermore, the visualized GSH after 60 min of transport by MALDI-MS imaging showed localization of intact GSH inside the intestinal wall. In vivo study found that ingested (13)C-GSH was rapidly converted to GSSG and accumulated in red blood cells and liver, but was little present in plasma. The ingested GSH has potent nutraceutical benefits for human health to improve oxidative stress and defense in human.

Keywords: Caco-2; LC-MS/MS; MALDI-MS imaging; glutathione; intestinal epithelial cell; transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Caco-2 Cells
  • Cell Wall / metabolism
  • Erythrocytes / metabolism
  • Female
  • Glutathione / metabolism*
  • Glutathione Disulfide / metabolism
  • HT29 Cells
  • Humans
  • In Vitro Techniques
  • Intestinal Mucosa / metabolism*
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Rats, Sprague-Dawley


  • Glutathione
  • Glutathione Disulfide