title: Sub-chronic treatment with pioglitazone exerts anti-convulsant effects in pentylenetetrazole-induced seizures of mice: The role of nitric oxide.
abstract: OBJECTIVE
  Pioglitazone delayed the development of seizure responses and shortened the duration of convulsion of genetically epileptic EL mice. The anti-epileptic effect of pioglitazone was attributed partly through the reduction of inflammatory responses and preventing apoptosis. There are also some reports showing that some pioglitazone effects mediate through nitric oxide. In this study we evaluated sub-chronic pioglitazone effects in two models of intravenous and intraperitoneal pentylenetetrazole-induced clonic seizures in mice.
  
  
  METHODS
  Different doses of pioglitazone were administered orally for 10 days in different groups of male mice. L-NAME, a non selective inhibitor of nitric oxide synthase, aminoguanidine, a selective inhibitor of inducible nitric oxide synthase, or L-arginine, a nitric oxide donor, was administered acutely or sub-chronically to evaluate the role of nitric oxide in pioglitazone anti-seizure effects.
  
  
  RESULTS
  We demonstrated that sub-chronic administration of pioglitazone exerted anti-convulsant effects in both models of intravenous and intraperitoneal pentylenetetrazole. Acute and sub-chronic pre-administration of L-NAME prevented the anti-convulsant effect of pioglitazone in both models of intravenous and intraperitoneal pentylenetetrazole. Aminoguanidine did not alter the anti-convulsant effect of pioglitazone in two models of intravenous and intraperitoneal pentylenetetrazole. Both acute and sub-chronic pre-treatment of mice with L-arginine exerted anti-convulsant effect when administered with a non effective dose of pioglitazone in intraperitoneal method. In intravenous method, acute administration of L-arginine with a non-effective dose of pioglitazone enhanced the seizure clonic latency.
  
  
  CONCLUSIONS
  Taken together, sub-chronic pioglitazone treatment exerts anti-convulsant effects in intravenous and intraperitoneal pentylenetetrazole-induced seizures of mice probably through induction of constitutive nitric oxide synthase.
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch and Pharmaceutical Sciences Research Center, Islamic Azad University, Tehran, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Shafaroodi
authors.forename: Leila
authors.initials: L
authors.lastname: Moezi
authors.forename: Hassan
authors.initials: H
authors.lastname: Ghorbani
authors.forename: Meysam
authors.initials: M
authors.lastname: Zaeri
authors.forename: Sara
authors.initials: S
authors.lastname: Hassanpour
authors.forename: Mahsa
authors.initials: M
authors.lastname: Hassanipour
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010433:Pentylenetetrazole / Q000633:toxicity; D000077205:Pioglitazone; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D045162:Thiazolidinediones / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D045162:Thiazolidinediones; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester; D010433:Pentylenetetrazole; D000077205:Pioglitazone