| Abstract |
Background: Sitagliptin is a specific dipeptidyl peptidase‐4 inhibitor that has established neuroprotective properties. Aim of this study: to investigate the potential the anti-epileptic effect of sitagliptin and its role in attenuating the neuronal changes that take place in the hippocampus. Material and methods: Adult male rats were used and alienated into; control and pilocarpine groups. The later was injected with a single intraperitoneal dose of pilocarpine (350 mg/kg) and monitor for 4 weeks for established chronic epilepsy. The animals were further subdivided into; pilocarpine untreated 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 increase in the hippocampal levels of nuclear factor-kappa-B (NF-kB) and malondialdehyde (MDA) in sitagliptin treated group in comparison to pilocarpine untreated group. Sitagliptin also induced a significant increase in the hippocampal levels of peroxisome gamma coactivator-1 alpha (PGC1α), 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 pilocarpine untreated group. 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.
KEYWORDS:Epilepsy; Endoplasmic reticulum stress; Hippocampus; Histopathology; Interneurons;Sitagliptin |
