| Autor: |
Elariny HA; Department of Pharmacology and Toxicology, College of Pharmacy, University of Hail, Hail 55476, Saudi Arabia.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo 35527, Egypt., Kabel AM; Pharmacology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt., Selim HMRM; Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia., Helal AI; Department of Histology and Cell Biology, Faculty of Medicine, Kafrelsheikh University, Kafr El-Shaikh 33516, Egypt., Abdelrahman D; Internal Medicine Department, College of Medicine, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia., Borg HM; Physiology Department, Faculty of Medicine, Kafrelsheikh University, Kafr El-Shaikh 33516, Egypt., Elkady MA; Pharmacology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt., Dawood LM; Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta 31511, Egypt., El-Badawy MF; Microbiology and Immunology Department, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt., Almalawi HFA; King Faisal Medical Complex, Taif Health Cluster, Taif 26513, Saudi Arabia., Arafa EA; College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab Emirates.; Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman 346, United Arab Emirates., Alsufyani SE; Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia., Arab HH; Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia. |
| Abstrakt: |
Background and Objectives: Alzheimer's disease (AD) is the most common neurodegenerative disorder in the world. Due to failure of the traditional drugs to produce a complete cure for AD, the search for new safe and effective lines of therapy has attracted the attention of ongoing research. Canagliflozin is an anti-diabetic agent with proven efficacy in the treatment of neurological disorders in which mitochondrial dysfunction, oxidative stress, apoptosis, and autophagy play a pathophysiological role. Elucidation of the potential effects of different doses of canagliflozin on AD induced by aluminium chloride in rats and exploration of the molecular mechanisms that may contribute to these effects were the primary objectives of the current study. Materials and Methods: In a rat model of AD, the effect of three different doses of canagliflozin on the behavioural, biochemical, and histopathological alterations induced by aluminium chloride was assessed. Results: Canagliflozin administered to aluminium chloride-treated animals induced dose-dependent normalisation in the behavioural tests, augmentation of the antioxidant defence mechanisms, inhibition of TXNIP/NLRP3 inflammasome signalling, modulation of the SIRT1/HMGB1 axis, interference with the pro-inflammatory and the pro-apoptotic mechanisms, and restoration of the mitochondrial functions and autophagy in the hippocampal tissues to approximately baseline values. In addition, canagliflozin exhibited an interesting dose-dependent ability to repress aluminium chloride-induced histopathological changes in the brain. Conclusions: The effects of canagliflozin on oxidative stress, mitochondrial functions, inflammatory pathways, and autophagy signals may open new gates towards the mitigation of the pathologic features of AD. |
