title: Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment in the kindling model of epilepsy.
abstract: OBJECTIVE
  Some conventional antiepileptic drugs induce oxidative stress and cognitive impairment which may limit their clinical applications. Ferulic acid is a phenolic phytochemical with antioxidant and neuroprotective properties that prompted us to evaluate its therapeutic potential in epilepsy which is usually associated with oxidative stress and cognitive decline.
  
  
  METHODS
  Male Wistar rats received 30mg/kg of pentylenetetrazole (PTZ) intraperitoneally (i.p.) once every alternate day until the development of kindling. The locomotor activity, elevated plus maze, and passive avoidance tests were performed. Oxidative stress was evaluated by the determination of brain malondialdehyde and reduced glutathione. The effects of pre-treatment with ferulic acid (25, 50, 75, and 100mg/kg, i.p.) against PTZ-kindled seizures, cognitive impairment, and oxidative stress were investigated.
  
  
  RESULTS
  Kindling was developed 34.18±1.54days after PTZ treatment which was associated with generalized tonic-clonic seizures (GTCS), myoclonic jerks, cognitive deficit, and oxidative stress. Ferulic acid at doses of 75 and 100mg/kg significantly reduced the seizure score, number of myoclonic jerks, cognitive decline and oxidative stress. Spontaneous locomotor activity did not significantly differ between the groups.
  
  
  CONCLUSIONS
  Ferulic acid exhibits antiepileptogenic effect and prevents oxidative stress and cognitive impairment induced by PTZ kindling. Therefore, this phenolic phytochemical appears as a promising adjuvant for antiepileptic drugs. Meanwhile, further experimental and clinical studies are required to provide insights into the cellular/molecular mechanism(s) underlying the action of ferulic acid.
authors.affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Neurological Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: p-hassanzadeh@razi.tums.ac.ir.
authors.forename: Parichehr
authors.initials: P
authors.lastname: Hassanzadeh
authors.affiliation: Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: arbabiavalelham@gmail.com.
authors.forename: Elham
authors.initials: E
authors.lastname: Arbabi
authors.affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Teheran, Iran. Electronic address: atyabifa@tums.ac.ir.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.affiliation: Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Teheran, Iran. Electronic address: Dinarvand@tums.ac.ir.
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D060825:Cognitive Dysfunction / Q000209:etiology / Q000517:prevention & control*; D003373:Coumaric Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000517:prevention & control
chemical_list: D000927:Anticonvulsants; D000975:Antioxidants; D003373:Coumaric Acids; C004999:ferulic acid; D010433:Pentylenetetrazole
keywords: Cognitive impairment; Ferulic acid; Oxidative stress; PTZ kindling; Rat