Glutathione protects against hypoxic/hypoglycemic decreases in 2-deoxyglucose uptake and presynaptic spikes in hippocampal slices

The effects of glutathione, its analogue: YM737 (N-(N-γ-l-glutamyl-l-cysteinyl) glycine l-isopropyl ester sulfate monohydrate), a monoester of glutathione, and N-acetyl-l-cysteine on hypoxia/hypoglycemia-induced decreases in CA1 presynaptic fiber spikes and 2-deoxyglucose uptake were investigated using rat hippocampal slices. The drugs were added to normal medium for 30 min before the incubation under hypoxic/hypoglycemic conditions (20 min), and, after a 3-h washout, presynaptic potential or 2-deoxyglucose uptake in hippocampal slices was measured. Treatment with glutathione, YM737 and N-acetyl-l-cysteine produced an attenuation of the hypoxia/hypoglycemia-induced decrease in presynaptic fiber spikes and 2-deoxyglucose uptake. The order of potency for neuroprotective action was YM737 ≥ N-acetyl-l-cysteine > glutathione. The present results suggest a role for glutathione in improving hypoxia/hypoglycemia-induced dysfunction of hippocampal regions.