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


CONCLUSIONS
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.
Pharmaceutical Sciences Branch and Pharmaceutical Sciences Research Center, Islamic Azad University, Tehran, Iran.
Hamed
H
Shafaroodi
Leila
L
Moezi
Ali
A
Fakhrzad
Mahsa
M
Hassanipour
Mehdi
M
Rezayat
Ahmad Reza
AR
Dehpour
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D000069059:Atorvastatin; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000009:adverse effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004830:Epilepsy, Tonic-Clonic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D006146:Guanidines / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism*; D010433:Pentylenetetrazole / Q000633:toxicity; D011758:Pyrroles / Q000627:therapeutic use*
D000927:Anticonvulsants; D003292:Convulsants; D004791:Enzyme Inhibitors; D006146:Guanidines; D006538:Heptanoic Acids; D011758:Pyrroles; D009569:Nitric Oxide; D000069059:Atorvastatin; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole