Effects of EUK-8, a synthetic catalytic superoxide scavenger, on hypoxia- and acidosis-induced damage in hippocampal slices.
Anoxia produces deleterious effects on synaptic transmission in the hippocampal slice preparation. A proposed source of damage is the superoxide radical (.O2-) produced during the earlier period of reoxygenation. The present study tested the effects of a synthetic, catalytic superoxide radical scavenger (EUK-8) on CA1 pyramidal cell responses elicited by electrical stimulation of the Schaffer-commissural pathway after severe anoxic episodes. Following reoxygenation, slices incubated with EUK-8 (50 microM) exhibited significantly better recovery of excitatory postsynaptic potentials (EPSPs) than control slices. In addition, repeated episodes of anoxia produced irreversible loss of synaptic transmission in the majority of control slices (93 +/- 7%, n = 15), compared to a small fraction in EUK-8-incubated slices (27 +/- 12%, n = 15). A thiobarbituric acid (TBA) test was used to assess the effect of EUK-8 on lipid peroxidation elicited in hippocampal slices by acidosis and lactic acid (pH 5.0 and 30 mM lactic acid). Incubation in the presence of EUK-8 totally prevented the increase in lipid peroxidation produced by acidosis and lactic acid in both the incubation medium and the slice homogenates. These results indicate that a superoxide scavenger like EUK-8 prevents damage produced by acidosis and anoxia in hippocampal slices and suggest the possibility of using this type of molecule under various pathological conditions.
Neuroscience Program, University of Southern California, Los Angeles 90089-2520.
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Musleh
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Bruce
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Malfroy
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Baudry
D000138:Acidosis / Q000473:pathology*; D000818:Animals; D005029:Ethylenediamines / Q000494:pharmacology*; D016166:Free Radical Scavengers; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D000860:Hypoxia / Q000473:pathology*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009942:Organometallic Compounds / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D005029:Ethylenediamines; D016166:Free Radical Scavengers; D009942:Organometallic Compounds; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; C090577:N,N'-bis(salicylideneamino)ethane-manganese(II); D013482:Superoxide Dismutase