Role of glutathione in repair of free radical damage in hippocampus in vitro.
Depletion of glutathione (GSH), an intrinsic antioxidant, increases vulnerability to free radical damage in a number of cell systems. This study investigates the role of GSH in limiting electrophysiological damage and/or recovery from free radical exposure in slices of guinea pig hippocampus. Synaptic potentials (PSPs) and population spikes (PSs) were recorded from field CA1. Free radicals were generated from 0.006% peroxide through the Fenton reaction. Analysis of the input-output curves showed that peroxide treatment decreased PSPs and impaired ability of the PSPs to generate PSs as previously reported. Recovery was nearly total within a half hour. Treatment with 5 mM buthionine sulfoximine (BSO) for 2 h depleted hippocampal GSH to 79.2% of control values. The extent of free radical damage was not increased. Recovery, however, was only partial. GSH was further depleted by oxidation with diamide or covalent bonding with dimethyl fumarate (DMF) immediately before and during the peroxide treatment. Neither diamide nor DMF treatment in BSO-incubated tissue enhanced peroxide-induced electrophysiological deficits. Following these treatments, however, tissue showed little recovery from free radical damage. We conclude that glutathione is essential for repair processes in hippocampal neurons exposed to oxidative damage.
Pellmar
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Physiology Department, Armed Forces Radiobiology, Research Institute, Bethesda, MD 20889-5145.
Roney
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Lepinski
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D000818:Animals; D019328:Buthionine Sulfoximine; D003958:Diamide / Q000494:pharmacology; D000069462:Dimethyl Fumarate; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005609:Free Radicals; D005650:Fumarates / Q000494:pharmacology; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000502:physiology*; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D005609:Free Radicals; D005650:Fumarates; D011838:Radiation-Sensitizing Agents; D003958:Diamide; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D000069462:Dimethyl Fumarate; D005978:Glutathione