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-gamma-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 > or = N-acetyl-L-cysteine > glutathione. The present results suggest a role for glutathione in improving hypoxia/hypoglycemia-induced dysfunction of hippocampal regions.
Shibata
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Tominaga
K
K
Watanabe
S
S
D000111:Acetylcysteine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003847:Deoxyglucose / Q000378:metabolism*; D004594:Electrophysiology; D016166:Free Radical Scavengers; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007003:Hypoglycemia / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*
D016166:Free Radical Scavengers; D017661:Receptors, Presynaptic; C058293:glutathione monoisopropyl ester; D003847:Deoxyglucose; D005978:Glutathione; D000111:Acetylcysteine