Effect of oxidant exposure on thiol status in the intestinal mucosa

The intestinal epithelium is likely to be exposed to oxidants derived from diet, bacterial metabolic products or endogenously formed cellular metabolites. Glutathione, being the major intracellular thiol, provides protection against oxidative injury. The present study looks at the effect of luminal exposure to oxidants on intestinal thiol status. Different oxidants were placed in the lumen of anesthetized rats for 30 min and the mucosal non-protein and protein-bound thiols were quantitated using HPLC. Oxidant exposure altered the thiol redox status and increased the oxidized glutathione (GSSG) level 6-7-fold and protein-bound reduced glutathione (GSH) 2-fold, whereas the non-protein GSH level remained the same or increased slightly. This could be due to either increased mucosal GSH synthesis or transport from circulation. After incubation with buthionine sulfoximine, a specific inhibitor of GSH synthesis, prior to oxidant exposure, the same increase in GSSG and GSH in the mucosa was seen. Oxidant exposure also decreased the plasma GSH level by 50%. The other cellular non-protein thiols, cysteine and cystine, did not change after luminal exposure to oxidants. These results suggest that oxidant exposure stimulates uptake of GSH from the circulation to maintain mucosal GSH.