Fish oil attenuates methylmalonate-induced seizures
Data
2013-07-01
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Artigo
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Methylmalonic acidemias are inherited metabolic disorders characterized by methylmalonate (MMA) accumulation and neurological dysfunction, including seizures. Dietary fatty acids are known as an important energy source and reduce seizure activity in selected acute animal models. This study investigated whether chronic treatment with fish oil or with oleic acid attenuates MMA-induced seizures and whether maintenance of Na+,K+-ATPase activity was involved in such an effect. Adult male Wistar rats were given fish oil (85 mg/kg), oleic acid (85 mg/kg) or vehicle (0.42% aqueous Cremophor EL (TM), 4 mL/kg/body weight/day), p.o., for 75 days. On the 73th day a cannula was implanted in the right lateral ventricle with electrodes over the parietal cortex for EEG recording. On the 76th day the animals were injected with NaCl (2.5 mu Lmol/2.5 mu L, i.c.v.), or with MMA (2.5 mu mol/2.5 mu L, i.c.v.), and seizure activity was measured by electroencephagraphic (EEG) recording with concomitant behavior monitoring. the effect of prostaglandin E-2 (PGE(2)) on Na+,K+-ATPase activity of slices of cerebral cortex from NaCl-injected animals was determined. Fish oil increased the latency to MMA-induced tonic-clonic seizures, reduced the mean amplitude of ictal EEG recordings, and prevented PGE(2)-induced decrease of Na+,K+-ATPase activity in cortical slices in vitro. Oleic acid decreased mean amplitude of ictal EEG recordings. the results support that fish oil decreases MMA-induced seizures. the decreased sensitivity of Na+,K+-ATPase to the inhibitory effect of PGE(2) in fish oil-treated animals may be related to the currently reported anticonvulsant activity. (C) 2013 Elsevier B.V. All rights reserved.
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Epilepsy Research. Amsterdam: Elsevier B.V., v. 105, n. 1-2, p. 69-76, 2013.