title: Chronic administration of atorvastatin induced anti-convulsant effects in mice: the role of nitric oxide.
abstract: Atorvastatin has neuroprotective effects, and there is some evidence that nitric oxide is involved in atorvastatin effects. In this study, we evaluated whether the nitrergic system is involved in the anticonvulsant effects of chronic atorvastatin administration. Intravenous and intraperitoneal pentylenetetrazol were used to induce seizures in mice. Chronic atorvastatin treatment significantly increased the seizure threshold which is induced by both intravenous and intraperitoneal pentylenetetrazol. Intraperitoneal pentylenetetrazol also decreased the incidence of tonic seizure and death in atorvastatin-treated groups. Chronic co-administration of a non-selective nitric oxide synthase inhibitor, l-NAME, or a selective inducible nitric oxide synthase inhibitor, aminoguanidine, with atorvastatin inhibited atorvastatin-induced anticonvulsant effects in intravenous model of pentylenetetrazol. Acute injection of l-NAME or aminoguanidine inhibited the anticonvulsant effects of atorvastatin in both models of intravenous- and intraperitoneal-pentylenetetrazol-induced seizures. In conclusion, we demonstrated that nitric oxide signaling probably through inducible nitric oxide synthase could be involved in the anticonvulsant effects of atorvastatin.
authors.affiliation: Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Moezi
authors.forename: Hamed
authors.initials: H
authors.lastname: Shafaroodi
authors.forename: Mahsa
authors.initials: M
authors.lastname: Hassanipour
authors.forename: Ali
authors.initials: A
authors.lastname: Fakhrzad
authors.forename: Sara
authors.initials: S
authors.lastname: Hassanpour
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D000069059:Atorvastatin; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006146:Guanidines / Q000008:administration & dosage; D006538:Heptanoic Acids / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism*; D010433:Pentylenetetrazole / Q000633:toxicity; D011758:Pyrroles / Q000008:administration & dosage*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013997:Time Factors
chemical_list: 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