The involvement of nitric oxide in the anti-seizure effect of acute atorvastatin treatment in mice

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Objectives: In addition to reducing the serum level of cholesterol, statins have various pleiotropic effects such as increasing nitric oxide and reducing oxidative stress, neuroinflammation, and neurotoxicity. Increasing evidence indicates that statins are neuroprotective in several conditions, including stroke, cerebral ischemia and traumatic brain injury. However, only a few studies have investigated whether statins modulate seizure activity.Methods: In the current study, we investigated whether acute treatment with atorvastatin alters the seizures induced by electroshock or pentylenetetrazole in mice. We also evaluated whether nitrergic system is involved in the effects of acute atorvastatin on seizure.Results: The results of the present study demonstrate that acute atorvastatin (10 and 20 mg/kg) treatment decreased the incidence of tonic seizure and death in electroshock-induced seizure model. We also showed that acute atorvastatin (10 mg/kg) treatment increased the clonic seizure threshold in pentylenetetrazole-seizure model. Acute L-NAME (5 mg/kg), a non-selective inhibitor of nitric oxide synthase, or aminoguanidine (100 mg/kg), a selective inhibitor of inducible nitric oxide synthase, administration prevented the anti-convulsant effect of atorvastatin in electroshock-induced seizure model. We also demonstrated that acute L-NAME (5 mg/kg) or aminoguanidine (100 mg/kg) administration decreased the enhanced clonic latency of clonic seizure threshold induced by atorvastatin in mice in pentylenetetrazole model.Discussion: In conclusion, anti-convulsant effect of atorvastatin was demonstrated in two seizure models of electroshock and intraperitoneal pentylenetetrazole. Nitric oxide release, probably through inducible nitric oxide synthase at least in part is responsible for this effect.