Antiepileptic effect of fisetin in iron-induced experimental model of traumatic epilepsy in rats in the light of electrophysiological, biochemical, and behavioral observations

Nutr Neurosci. 2017 May;20(4):255-264. doi: 10.1080/1028415X.2016.1183342. Epub 2016 May 19.

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.

Conclusion: This study demonstrated the antiepileptic action of fisetin in iron-induced model of epileptic rats by inhibiting oxidative stress.

Keywords: Epilepsy; Fisetin; K+-ATPase; Lipid peroxidation; Morris water maze; Na+; Open-field test; Oxidative stress.

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Behavior, Animal / drug effects*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Disease Models, Animal
  • Electroencephalography
  • Electrophysiological Phenomena / drug effects*
  • Epilepsy, Post-Traumatic / chemically induced
  • Epilepsy, Post-Traumatic / drug therapy*
  • Flavonoids / pharmacology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Iron
  • Lipid Peroxidation / drug effects
  • Male
  • Oxidative Stress / drug effects
  • Phytochemicals / pharmacology
  • Rats
  • Rats, Wistar
  • Seizures / chemically induced
  • Seizures / drug therapy
  • Sodium-Potassium-Exchanging ATPase / metabolism

Substances

  • Anticonvulsants
  • Flavonoids
  • Phytochemicals
  • Iron
  • Sodium-Potassium-Exchanging ATPase
  • fisetin