Does elevated glutathione protect the cell from H2O2 insult?

Utilizing glutathione ethyl ester (GSH-EE), the glutathione (GSH) level of lens epithelial cells can be increased as much as 1.9-fold. The epithelial cells maintain the additional GSH in the reduced form. This system was utilized to examine the relative effectiveness of cells with elevated GSH to withstand H2O2 insult. Three parameters were investigated, 86Rb accumulation, a measure of membrane function, ATP levels, an indication of overall metabolism and glyceraldehyde-3-phosphate dehydrogenase (GPD) activity, indicating intracellular enzyme susceptibility to oxidative insult. Under oxidative stress, much of the GSH is in the oxidized form but upon removal of the stress, rapidly returns to the reduced state. However, a loss of approximately 20% in GSH equilibrium levels has been consistently observed. Elevated GSH does not significantly increase the cells' ability to withstand or recover from oxidative stress. Indeed, elevated GSH was found to be somewhat deleterious, causing a decreased ability to recover from oxidative insult. However, in the case of GPD, a significant protection of activity was observed. The overall conclusion is that elevating intracellular GSH concentration does not increase the cells' overall ability to withstand oxidative damage.