Sitagliptin Modulated Hippocampal Inflammation, Endoplasmic Reticulum Stress and Inhibitory Interneurons in a Rat Model of Epilepsy
Journal Title: International Journal of Medical and Health Sciences - Year 2018, Vol 7, Issue 2
Abstract
Background: Sitagliptin is a specific dipeptidyl peptidase‐4 inhibitor that has established neuroprotective properties. Aim of this study: To investigate the potential anti-epileptic effect of sitagliptin and its role in attenuating the neuronal changes that take place in the hippocampus. Material and methods: Adult male wistar rats were used and alienated into; control group and pilocarpine group. The later was injected with a single intraperitoneal dose of pilocarpine (350 mg/kg) and was monitored for 4 weeks for established chronic epilepsy. The rats of pilocarpine group were further subdivided into; the untreated pilocarpine group and sitagliptin (30 mg/kg/day, orally, for 8 weeks) treated group. After the experimental duration, the hippocampus was dissected for biochemical and structural analysis. Results: The current data revealed a significant decrease in the hippocampal levels of nuclear factor-kappa-B (NF-kB) and malondialdehyde (MDA) in sitagliptin treated group in comparison to untreated Pilocarpinegroup. Sitagliptin also induced a significant increase in the hippocampal levels of Peroxisome proliferator-activated receptor gamma (PPARγ) coactivator 1α (PGC1α), reduced glutathione (GSH) and (C/EBP)-homologous protein (CHOP). Additionally, sitagliptin counteracted the damaging effect of pilocarpine on the cellular structure of hippocampus, where most of The CA1 pyramidal cells maintained the normal rounded vesicular nuclei with less degree of vacuolation compared to untreated Pilocarpinegroup. Moreover, sitagliptin treated group showed a significant increase in parvalbumin and somatostatin-positive interneurons which are the main GABAergic inhibitory interneurons involved in epilepsy. Conclusion: The measured parameters exposed the neuroprotective role of sitagliptin against the hippocampal inflammation, endoplasmic reticulum stress and the histopathological alterations, that suggest therapeutic applications of sitagliptin in cases of epilepsy.
Authors and Affiliations
Rasha Osama El-Esawy, NohaGamal Bahey, Omnia Safwat El-Deeb, RowidaRaafat Ibrahim
Keywords
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