title: Anticonvulsive Effects of Licofelone on Status Epilepticus Induced by Lithium-pilocarpine in Wistar Rats: a Role for Inducible Nitric Oxide Synthase.
abstract: OBJECTIVE
  Status epilepticus (SE) is a neurological disorder with high prevalence and mortality rates, requiring immediate intervention. Licofelone is a cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitor, which its effectiveness to treat osteoarthritis has been approved. Increasing evidence suggests an involvement of COX and LOX enzymes in epileptic disorders. Thus, in the present study we investigate possible effects of licofelone on prevention and termination of SE. We also evaluated whether the nitrergic system could participate in this effect of licofelone.
  
  
  METHODS
  We have utilized lithium-pilocarpine model of SE in adult Wistar rats to assess the potential effect of licofelone on seizure susceptibility. Licofelone was administered 1 h before pilocarpine. To evaluate probable role of nitric oxide (NO) system, L-arginine (60 mg/kg, i.p.), as a NO precursor; L-NAME (15 mg/kg, i.p.), as a non-selective nitric oxide synthase (NOS) inhibitor; aminoguanidine (100 mg/kg, i.p.), as an inducible NOS (iNOS) inhibitor and 7-nitroindazole (60 mg/kg, i.p.), as a neuronal NOS inhibitor were injected 15 min before licofelone. Also, licofelone and diazepam 10 mg/kg were administered 30 minutes after onset of SE.
  
  
  RESULTS
  Pre-treatment with licofelone at the dosage of 10 mg/kg, significantly prevented the onset of SE in all subjects (p< 0.001). L-arginine significantly inverted this anticonvulsant effect (p< 0.05). However, L-NAME and aminoguanidine, potentiated the anticonvulsant effect of licofelone (p< 0.05,p< 0.01). Licofelone could not terminate seizures after onset which was terminated by diazepam.
  
  
  CONCLUSIONS
  Our findings showed that anticonvulsive effects of licofelone on SE could be mediated by iNOS. Also, we suggest that COX/5-LOX activation is possibly required in the initial stage of onset but SE recruits extra excitatory pathways with prolongation.
authors.affiliation: Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyyed Majid
authors.initials: SM
authors.lastname: Eslami
authors.affiliation: Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Mobin
authors.initials: MM
authors.lastname: Moradi
authors.affiliation: Department of Neurology, University of Massachusetts Medical Center, Worcester, MA, USA.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghasemi
authors.affiliation: Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
keywords: 5-lipoxygenase; Cyclooxygenase; Licofelone; Nitric oxide synthase; Status epilepticus