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.

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

Keywords:

• Fisetin
• Epilepsy
• Oxidative stress
• Na⁺
• K⁺-ATPase
• Lipid peroxidation
• Morris water maze
• Open-field test

Acknowledgement

Financial support from Department of Biotechnology (DBT), Government of India, New Delhi, India for undertaking the present work is gratefully acknowledged.

Disclaimer statements

Contributors Conceiving and designing the study: Deepak Sharma, Jharana Das. Obtaining funding and/or ethics approval: Deepak Sharma. Collecting the data: Jharana Das. Analysing the data: Jharana Das. Interpreting the data: Jharana Das, Deepak Sharma, Rameshwar Singh. Writing the article in whole or in part: Jharana Das, Rameshwar Singh, Deepak Sharma. Revising the article: Jharana Das, Rameshwar Singh, Deepak Sharma.

Funding Department of Biotechnology, Ministry of Science and Technology, Government of India, New Delhi, India (BT/PR4993/MED/30/914/2012).

Conflict of interest None.

Ethics approval This study has received ethical approval from the Committee for the Purpose of Control and Supervision of Experimental Animals (CPCSEA) and the Institutional Animal Ethical Committee of Jawaharlal Nehru University, New Delhi, India.