title: Antiepileptic effect of fisetin in iron-induced experimental model of traumatic epilepsy in rats in the light of electrophysiological, biochemical, and behavioral observations.
abstract: BACKGROUND
  Traumatic epilepsy is defined by episodes of recurring seizures secondary to severe brain injury. Though drugs are found effective to control seizures, their long-term use have been observed to increase reactive oxygen species in animals. Flavonoid fisetin, a natural bioactive phytonutrient reported to exert anticonvulsive effect in experimental seizure models. But, trauma-induced seizures could not be prevented by anticonvulsants was reported in some clinical studies.
  
  
  OBJECTIVE
  To study the effect of fisetin on epileptiform electrographic activity in iron-induced traumatic epilepsy and also the probable reason behind the effect in rats.
  
  
  METHODS
  Fisetin pretreatment (20 mg/kg body wt., p.o.) of rats for 12 weeks were chosen followed by injecting iron (5 µl, 100 mM) stereotaxically to generate iron-induced epilepsy. Experimental design include electrophysiological study (electroencephalograph in correlation with multiple unit activity (MUA) in the cortex and CA1 subfield of the hippocampus; spectral analysis of seizure and seizure-associated behavioral study (Morris water maze for spatial learning, open-field test for anxiety) and biochemical study (lipid peroxidation, Na+,K+-ATPase activity) in both the cortex and the hippocampus.
  
  
  RESULTS
  Fisetin pretreatment was found to prevent the development of iron-induced electrical seizure and decrease the corresponding MUA in the cortex (*P˂0.05) as well as in the hippocampus (***P˂0.001). Fisetin pretreatment decreased the lipid peroxides (*P˂0.05) and retained the Na+,K+-ATPase activity (*P˂0.05) which was found altered in the epileptic animals and also found to attenuate the seizure-associated cognitive dysfunctions.
  
  
  CONCLUSIONS
  This study demonstrated the antiepileptic action of fisetin in iron-induced model of epileptic rats by inhibiting oxidative stress.
authors.affiliation: a Laboratory of Neurobiology, School of Life Sciences, Jawaharlal Nehru University , New Delhi 110067 , India.
authors.forename: Jharana
authors.initials: J
authors.lastname: Das
authors.affiliation: a Laboratory of Neurobiology, School of Life Sciences, Jawaharlal Nehru University , New Delhi 110067 , India.
authors.forename: Rameshwar
authors.initials: R
authors.lastname: Singh
authors.affiliation: a Laboratory of Neurobiology, School of Life Sciences, Jawaharlal Nehru University , New Delhi 110067 , India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004569:Electroencephalography; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D004834:Epilepsy, Post-Traumatic / Q000139:chemically induced / Q000188:drug therapy*; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007501:Iron; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D064209:Phytochemicals / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D005419:Flavonoids; D044948:Flavonols; D064209:Phytochemicals; D007501:Iron; D000254:Sodium-Potassium-Exchanging ATPase; C017875:fisetin
keywords: Epilepsy; Fisetin; K+-ATPase; Lipid peroxidation; Morris water maze; Na+; Open-field test; Oxidative stress