Antiepileptic effects of allopurinol on EL mice are associated with changes in SOD isoenzyme activities.
We have investigated the potential antiepileptic action of superoxide dismutase (SOD) activities in the brain of the epileptic mutant EL mouse. EL mice which experienced frequent seizures (EL[s]) had abnormally low levels of SOD isoenzyme activity in the hippocampal area. Once epileptogenicity was established in these animals, activity of cyanide-sensitive Cu,Zn-SOD was maintained at significantly lower levels than in control mice. However, cyanide-insensitive Mn-SOD activity was not different from non-epileptic controls. In EL mice which had not experienced seizure provoking stimulations and exhibited no seizures (EL[ns]) there was moderately lower levels of SOD isoenzyme activities compared to controls. In spite of the low level of Cu,Zn-SOD activity in EL[s] mice, the Cu,Zn-SOD protein content was high in the hippocampus of these animals, suggesting that inactive Cu,Zn-SOD might be induced during development. After allopurinol (ALP) was given orally to EL[s] mice, Cu,Zn-SOD activities increased dramatically in the hippocampus and seizure activity was decreased. Even after 48 h, when antiepileptic action of ALP was lost, the SOD activity was maintained at the high level associated with initial ALP administration. EL[s] mice also showed DNA fragmentation in the hippocampal CA1 region and the parietal cortex, detected with in situ terminal transferase-mediated dUTP nick labeling with the aid of alkaliphosphatase or peroxidase. The degree of DNA fragmentation was less severe in EL[ns] mice. We propose that abnormalities in region specific Cu,Zn-SOD isoenzyme activity might produce free radicals, leading to DNA fragmentations and cell loss. This might contribute to hippocampal epileptogenesis in EL mice.
Department of Neurophysiology, Tokyo Institute of Psychiatry, Japan.
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Murashima
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Kasamo
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Suzuki
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008818:Mice, Neurologic Mutants; D009928:Organ Specificity; D010296:Parietal Lobe / Q000201:enzymology; D012640:Seizures / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism*; D013997:Time Factors
D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D000493:Allopurinol; D013482:Superoxide Dismutase