Sericin alleviates pentylenetetrazole kindling epilepsy and associated comorbidities via modulation of GABA-T enzyme and mitochondrial activity

Abstract

Objective: To assess the effect of sericin against pentylenetetrazole (PTZ) kindling epilepsy and its associated comorbidities. Methods: Epilepsy was induced with PTZ at the dose of 30 mg/kg i.p. on alternative days for 25 days in rats. Sericin was administered orally at the doses of 250, 500, and 1 000 mg/kg for 35 days. The behavioral activities were performed using an elevated plus maze, forced swim test, and Morris water maze test. A PTZ challenge test was conducted on day 32. On day 35, rats were sacrificed to perform oxidative stress, mitochondrial dysfunction, neuroinflammation, neurotransmitters, GABA-T activity, and histopathological analyses. Results: Sericin at 500 and 1 000 mg/kg significantly reduced behavioral changes and neuroinflammatory cytokines, as well as improved oxidative stress, mitochondrial enzyme complex activity, neurotransmitter level, and GABA-T enzymatic activity (P<0.05). Moreover, sericin improved the neuronal survival altered by PTZ kindling in rat hippocampus. Conclusions: Sericin mitigates epilepsy-associated secondary complications possibly by the modulation of mitochondrial enzyme complexes and GABA-T enzymatic activity.

Keywords

Pentylenetetrazole / Sericin / GABA-T / Epilepsy / Anxiety / Cognitive impairment

Acknowledgments

The authors are highly thankful to Mr. Parveen Garg, Chairman, and Prof. (Dr.) G.D. Gupta, Director-cum-Principal, ISF College of Pharmacy, Moga, and I. K. Gujral Punjab Technical University, Jalandhar, Punjab, India for providing an excellent research platform. The authors extend their special thanks to Prof. (Dr.) Y.K. Gupta, President, AIIMS Bhopal, and Jammu for spending their valuable time in reading and editing the manuscript.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

The authors received no extramural funding for the study.

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

All authors contributed to the study conception and design. Study design, experimental work, data collection, data analysis and writing were performed by SG. RKN contributed to literature analysis, critical revision and manuscript drafting. Manuscript drafting, final analysis and approval were performed by SS. All authors read and approved the final manuscript.

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