Evaluation of repeated ghrelin administration on seizures, oxidative stress and neurochemical parameters in pentyleneterazole induced kindling in rats

Abstract

Introduction: Epileptic seizures are thought to be caused by the impaired balance between excitatory (glutamate) and inhibitor [gamma amino butyric acid (GABA)] neurotransmitters in the brain. Neuropeptides have potent modulator properties on these neurotransmitters.Objective: Ghrelin exerts anticonvulsant effects in an acute pentylenetetrazole (PTZ) model. However, the effect of repeated ghrelin injections in chronic pentylenetetrazole kindling model is not known. In this study, the effects of repeated ghrelin administration on seizure scores, working memory, locomotor activity, oxidative biomarkers, and neurochemical parameters in PTZ kindling in rats was examined.Methods: For this purpose, 35 mg/kg of PTZ was administered intraperitoneally to the experimental groups. The rats also received physiological saline/diazepam or ghrelin before each PTZ injection. After behavioural analysis (Y-maze, rotarod, and locomotor activity tests), biochemical and neurochemical analyses were conducted using ELISA.Results: PTZ administration induced progression in the seizure scores and all of the rats in the PS + PTZ group were kindled with the 20^th injection. Ghrelin treatment significantly reduced the seizure scores. The difference among the groups in terms of the Y-maze, locomotor activity, and rotarod tests was nonsignificant. PTZ administration significantly decreased the brain GABA, CAT, and AChE levels, and increased the MDA, NO, and protein carbonyl levels. Repeated ghrelin treatment ameliorated the GABA, AChE, CAT, MDA, NO, and protein carbonyl levels.Conclusion: Taken together, the results indicated that repeated ghrelin treatment had antioxidant, and anticonvulsant activity on PTZ kindling in rats.

Keywords:

• Chronic epilepsy model
• ghrelin
• kindling
• neuropeptide
• pentylenetetrazole (PTZ)
• seizure

Acknowledgment

The authors would like to thank for the financial support the Scientific and Technological Research Council of Turkey TUBITAK projects (project no: 118S201).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the [Scientific and Technological Research Council of Turkey TUBITAK projects] under Grant [number 118S201].