Resveratrol suppressed seizures by attenuating IL-1β, IL1-Ra, IL-6, and TNF-α in the hippocampus and cortex of kindled mice

Abstract

Objective: There is an urge to identify new molecules which can modulate process of epileptogenesis, since currently available drugs act symptomatically and one-third of the patients remain refractory to the disease. Hence, the present study was conducted to evaluate the effects of Resveratrol (RESV) on epileptogenesis in pentylenetetrazole (PTZ)-induced kindling in mice.

Method: Swiss albino mice were administered RESV (10, 20 and 40 mg/kg,p.o) in acute study. On the seventh day animals were subjected to various neurological and neurobehavioral tests viz, Increasing Current Electroshock Test (ICES), PTZ-induced seizures, passive avoidance response, and elevated plus maze test. For the development of kindling PTZ was administered in a dose of 25 mg/kg, i.p. on every alternate day and RESV in all the three doses was administered daily. Seizure score was continuously monitored till the development of kindling and cognition tests were performed in the end of the study. The animals were sacrificed and levels of inflammatory biomarkers viz., IL-1β, interleukin-1 receptor antagonist (IL1-Ra), IL-6, and TNF-α were assessed in the hippocampus and cortex of the kindled animals.

Results: RESV in all three doses increased the seizure threshold to hind limb extension in the ICES test. RESV in all the tested doses suppressed the development of kindling and reduced the levels of IL-1β, IL1-Ra, IL-6, and TNF-α in kindled mice.

Conclusion: RESV suppressed the development of kindling in mice and decreased the levels of inflammatory biomarkers in their hippocampus. RESV modified brain inflammation during epileptogenesis and found to possess nootropic activity in the kindled mice.

Keywords:

• Resveratrol
• Kindling
• Epileptogenesis
• Inflammatory biomarkers
• Cognition

Acknowledgements

We are thankful to Department of Science and Technology (DST), Government of India for providing INSPIRE Fellowship to Ubedul Hoda.

Disclaimer statements

Contributors All authors contributed equally.

Funding None.

Conflict of interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Ethics approval The animals were taken care of in accordance with the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India. Prior approval for the study was obtained from the Institutional Animal Ethics Committee, Jamia Hamdard, New Delhi.

ORCID

Ubedul Hoda http://orcid.org/0000-0002-6630-2381

Suhel Parvez http://orcid.org/0000-0002-6318-6506