Favorable effects of vildagliptin on metabolic and cognitive dysfunctions in streptozotocin-induced diabetic rats
| Autor: | Noha M. Shafik, Maha M. El Batsh, Manal El Batch, Ibrahim Younos |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Pyrrolidines Adamantane medicine.disease_cause Diabetes Mellitus Experimental Rats Sprague-Dawley chemistry.chemical_compound Cognition High-density lipoprotein Internal medicine Diabetes mellitus Nitriles medicine Animals Vildagliptin Cognitive decline Pharmacology Brain-derived neurotrophic factor Behavior Animal Tumor Necrosis Factor-alpha business.industry Brain-Derived Neurotrophic Factor Body Weight Transcription Factor RelA Brain medicine.disease Malondialdehyde Streptozotocin Rats Oxidative Stress Neuroprotective Agents Endocrinology chemistry business Oxidative stress medicine.drug |
| Zdroj: | European Journal of Pharmacology. 769:297-305 |
| ISSN: | 0014-2999 |
| Popis: | Progression of diabetes mellitus is accompanied by metabolic disorders together with psychological deficits including cognitive dysfunctions. Herein, we used a murine streptozotocin (STZ)-induced diabetes to investigate the beneficial effects of vildagliptin not only on metabolic abnormalities, but also on diabetes-induced cognitive decline. Sixty rats were divided randomly and equally into 2 groups; one remains normal and the other serves as STZ- induced diabetic. Both groups were further divided equally into 2 groups; one received vehicle and the other received oral vildagliptin for 8 weeks. Cognitive behavior was assessed using novel object recognition test. Blood samples were collected to measure metabolic parameters and dipeptidyl peptidase (DPP)-IV activity. Brains were removed and investigated for the levels of inflammatory and oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-α (TNF-α), in addition to brain-derived neurotrophic factor (BDNF) and relative expression of nuclear factor kappa B (NF-κB)/p65. Treatment of STZ-induced diabetic rats with vildagliptin increased their body weight and corrected diabetes-induced memory and learning impairment. Moreover, vildagliptin significantly decreased serum levels of glucose and lipids (except high density lipoprotein) together with brain MDA, TNF-α, serum DPP-IV activities and NF-κB/p65 gene expression. On the other hand, vildagliptin significantly increased brain BDNF, SOD as well as serum insulin. Results suggested that vildagliptin has a protective role in counteracting both metabolic abnormalities and memory deficits in diabetic rats, possibly via its anti-hyperglycemic, anti-inflammatory, antioxidant effects, together with reduction of brain NF-κB/p65 over expression. |
| Databáze: | OpenAIRE |
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