Transepithelial transport of glutathione in vascularly perfused small intestine of rat.

We used an in situ closed-loop vascular perfusion of rat small intestine to see whether intact glutathione (GSH) was transported from the lumen into the mesenteric circulation. Results using [3H] GSH showed radiolabel appearance in the perfusate, and high-performance liquid chromatography analysis confirmed that the transported radiolabeled species was intact GSH. Transepithelial transport was Na+ dependent, where Na+-free solutions on the luminal side inhibited transport but in the vasculature stimulated transport. Transport was inhibited by the GSH analogues ophthalmic acid and gamma-glutamylglutamate when added to the lumen. Probenecid caused inhibition only when added on the vascular side, suggesting that the transport systems on the two poles of the cells may be different. In vivo studies with GSH administration via stomach gavage caused marked increases in plasma GSH concentrations. These results establish that transepithelial transport of intact GSH occurs in rat small intestine. This process may allow dietary or biliary derived GSH to be utilized by various cell types that can take up intact GSH from the plasma. Moreover, the results show that oral administration of GSH may be therapeutically useful.