Novel Protection by Omega-3-FAs against Strychnine-Induced Tonic-Convulsion in Mice: Synergy with Carbamazepine
Abstract
Background/Aim: The utility of ω-3-FAs (DHA and EPA) against epilepsy was evident in clonic-convulsion animal-models, in their chronic- than acute-modes. However, their efficacy against tonic-convulsion-models remained unclear. Besides, while some-antiepileptics (AEDs), like carbamazepine (CBZ), adversely impacted the bioavailability of dietary ω-3-FAs, it remains unclear whether co-ω-3-FAs may change efficacy/blood-levels of CBZ. This work investigated the capacity of both acute- versus chronic-regimens of ω-3-FAs to: 1) alleviate the-tonic, strychnine-induced convulsions in mice, and 2) synergize with CBZ-evoked anti-tonic-convulsions, and then further-probe whether this has altered plasma-CBZ levels (clearance).
Methods: Both acute (1.0 hr)- and chronic (14 day)-regimens of the ω-3-FAs, DHA and EPA (120-1000mg/kg p.o.), were administered in a mouse strychnine convulsion-model (2mg/kg i.p.), and seizure frequency, latency and animal-survival were determined versus the positive-control CBZ (12mg/kg p.o). Further, synergy between submaximal-doses of DHA(EPA) and CBZ was verified. Lastly, pharmacokinetic interaction was verified in rats by determining plasma CBZ-levels in the presence- and-absence of ω-3-FAs.
Results: Both DHA and EPA dose-dependently enhanced seizure latency (2-folds) and protected mice against strychnine-induced convulsion (up to 75%). Besides, interestingly, similar responses and animal-survival rates obtained in acute and chronic models. Moreover, either…
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