SITAGLIPTIN MITIGATES SCOPOLAMINE-INDUCED NEUROCOGNITIVE DEFICITS VIA ACTIVATION OF Nrf2/HO-1 PATHWAY AND IMPROVED MITOCHONDRIAL ACTIVITY | ||
| The Egyptian Journal of Forensic Sciences and Applied Toxicology | ||
| Volume 25, Issue 1, March 2025, Pages 45-62 PDF (1.55 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/ejfsat.2024.335654.1355 | ||
| Authors | ||
| suzan A Khodir* 1; Ahmad Gaafar2; Basma Mostafa3; Noha Abd El-aziz4; amany Elfakhrany5; Shehab Hassaan6; Mai Hassan7; Soha Abd EL-Khalek8; Menna Allah El Menyawi9 | ||
| 1physiology department, faculty of medicine, menoufia university | ||
| 2Medical Physiology Department, Faculty of Medicine, Menoufia University | ||
| 3Medical Biochemistry and Molecular Biology Department, Faculty of medicine, Menoufia University | ||
| 4Anatomy and Embryology Department, Faculty of Medicine, Menoufia University | ||
| 5Clinical Pharmacology Department, Faculty of medicine, Menoufia University | ||
| 6Psychiatry department, Sulaiman Alrajhi University, Al Bukayriyah, Saudi Arabia. Psychiatry department, faculty of medicine, Assiut University, Assiut, Egypt. | ||
| 7Anatomy and Embryology Department, Faculty of Medicine, Benha University | ||
| 8Forensic Medicine and Clinical Toxicology department, Faculty of Medicine, Menoufia University | ||
| 9Medical Physiology Department, Faculty of Medicine, Suez Canal University, Ismailia | ||
| Abstract | ||
| Background: Rats' memory is hampered by the muscarinic receptor antagonist scopolamine (Scop), which inhibits cholinergic neurotransmission. Objectives: to assess the protective impact of sitaglibtin and its underlying processes in neurocognitive impairments brought on by Scop. Methodology: Thirty adult male albino rats were divided into three groups: control, Scop, and Scop+STG (10/group). Rats were evaluated neurocognitively. The following were measured: BDNF, Nrf2, HO-1, citrate synthase (CS) activity, acetylcholine, MDA, SOD, TNF-α, interleukin (IL)-6, IL-10, and amyloid β 42 (Aβ42). Additionally, hippocampal histological and immunohistochemical analyses were performed. Results Along with significantly greater levels of MDA, TNF-α, IL-6, acetylcholine, and Aβ 42, as well as GFAP and Caspase-3 hippocampus immunoreaction, the Scop group also showed a decline in cognitive performance compared to control. Additionally, it down-regulated BDNF, Nrf2, and HO-1 gene expression in the hippocampus and markedly decreased IL-10, SOD, and CS activity. The Scop+STG showed a considerable amelioration in the neurocognitive deficits caused by Scop. Conclusion: In addition to up-regulating Nrf2 and HO-1 gene expressions, sitagliptin has a beneficial protective impact against Scop-induced cognition impairments through anti-oxidant, anti-inflammatory, enhanced mitochondrial activity, prevention of apoptosis, and neurotrophic actions. | ||
| Keywords | ||
| BDNF; Caspase-3; HO1; Nrf2; Scopolamine; Sitagliptin | ||
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