Total body glutathione depletion induces oxidative stress and disrupts the immune function in mice

The effect of total body glutathione (GSH) depletion induced by L-buthionine- (S,R)-sulfoximine (BSO) treatment on the murine immune system has not been studied previously. BSO was administered via drinking water for 14 days to induce total body GSH depletion. A significant decrease in total GSH (TGSH) of the immune organs such as spleen, liver, peritoneal macrophages as well as blood was observed. The proliferative response of splenocytes against different types of mitogens was significantly decreased in GSH-depleted mice compared to controls. The expression of several antioxidant enzymes was studied in both treated and control mice. No significant change was seen in major antioxidant enzymes; manganese superoxide dismutase and catalase. However, the expression of heme oxygenase-1 was increased in both liver and spleen in BSO-treated mice. Total body GSH depletion also increased lipid peroxidation as demonstrated by higher levels of malondialdehyde in BSO-treated mice. All the above-mentioned changes were reversed to near normal 14 days post termination of BSO treatment. These results demonstrate that TGSH depletion induces oxidative stress and adversely affects the function of the murine immune system.