Carnosine ameliorates cognitive deficits in streptozotocin-induced diabetic rats: Possible involved mechanisms |
| |
Institution: | 1. Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Misr International University, Cairo, Egypt;2. Pharmacology and Toxicology Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt (FUE), Cairo, Egypt.;3. Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt;4. Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt;5. Biochemistry and Clinical Pharmacy Department, Faculty of Pharmacy, Misr International University, Cairo, Egypt |
| |
Abstract: | Diabetic patients are at increased risk to develop cognitive deficit and senile dementia. This study was planned to assess the benefits of chronic carnosine administration on prevention of learning and memory deterioration in streptozotocin (STZ)-diabetic rats and to explore some of the involved mechanisms. Rats were divided into 5 groups: i.e., control, carnosine100-treated control, diabetic, and carnosine-treated diabetics (50 and 100 mg/kg). Carnosine was injected i.p. at doses of 50 or 100 mg/kg for 7 weeks, started 1 week after induction of diabetes using streptozotocin. Treatment of diabetic rats with carnosine at a dose of 100 mg/kg at the end of the study lowered serum glucose, improved spatial recognition memory in Y maze, improved retention and recall in elevated plus maze, and prevented reduction of step-through latency in passive avoidance task. Furthermore, carnosine at a dose of 100 mg/kg reduced hippocampal acetylcholinesterase (AChE) activity, lowered lipid peroxidation, and improved superoxide dismutase (SOD) activity and non-enzymatic antioxidant defense element glutathione (GSH), but not activity of catalase. Meanwhile, hippocampal level of nuclear factor-kappaB (NF-κB), tumor necrosis factor α (TNF-α), and glial fibrillary acidic protein (GFAP) decreased and level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) increased upon treatment of diabetic group with carnosine at a dose of 100 mg/kg. Taken together, chronic carnosine treatment could ameliorate learning and memory disturbances in STZ-diabetic rats through intonation of NF-κB/Nrf2/HO-1 signaling cascade, attenuation of astrogliosis, possible improvement of cholinergic function, and amelioration of oxidative stress and neuroinflammation. |
| |
Keywords: | Diabetes mellitus Streptozotocin Carnosine Learning and memory Cognition |
本文献已被 ScienceDirect 等数据库收录! |
|