| Autor: |
Mohammad HMF; Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.; Center of Excellence in Molecular and Cellular Medicine (CEMCM), Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt., Eladl MA; Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates., Abdelmaogood AKK; Department of Clinical and Chemical Pathology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt., Elshaer RE; Pathology Department, Faculty of Medicine (Boys), Al-Azhar University, Cairo 11884, Egypt., Ghanam W; Department of Pathology, Faculty of Medicine, Suez University, Suez 43533, Egypt., Elaskary A; Ophthalmology Department, Al-Azher Asyut Faculty of Medicine for Men, Asyut 71524, Egypt., Saleh MAK; Ophthalmology Department, Al-Azher Asyut Faculty of Medicine for Men, Asyut 71524, Egypt., Eltrawy AH; Department of Anatomy and Embryology, Faculty of Medicine, Alexandria University, Alexandria 21526, Egypt.; Department of Anatomy, Faculty of Medicine, University of Tabuk, Tabuk 71451, Saudi Arabia., Ali SK; Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt., Moursi SMM; Medical Physiology Department, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt., Bilasy SE; College of Dental Medicine, California Northstate University, 9700 Taron Dr., Elk Grove, CA 95757, USA.; Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt., Zaitone SA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk 71451, Saudi Arabia.; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt., Alzlaiq WA; Department of Clinical Pharmacy, College of Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia., Atteya H; Department of Pharmacy Practice and Clinical Pharmacy, Faculty of Pharmacy, Future University in Egypt, Cairo 11835, Egypt.; Department of Medical Pharmacology, Faculty of Medicine, Cairo University, Giza 12613, Egypt. |
| Abstrakt: |
The possible impact of topiramate against diabetic retinopathy (DREN) and its molecular mechanisms in relation to the nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome has not been studied before. Thus, in the present study, we aimed to utilize a computational approach to investigate the possible protective effect of topiramate on experimental DREN and explore its impact on NLRP3/interlukin-1β signaling and brain-derived neurotrophic factor (BDNF) expression. Male albino mice were distributed to four experimental groups and assigned the following categorizations: (i) saline, (ii) diabetic, (iii) diabetic + topiramate 10 mg/kg and (iv) diabetic + topiramate 30 mg/kg. We observed shrinkage of total retinal thickness and elevation in retinal glutamate, malondialdehyde, NLRP3 and interlukin-1β but decreased glutathione (GSH) levels in the diabetic mice. Additionally, retinal ultra-structures in the diabetic group showed abnormalities and vacuolations in the pigmented epithelium, the photoreceptor segment, the outer nuclear layer, the inner nuclear layer and the ganglion cell layer (GCL). Mice treated with topiramate 10 or 30 mg/kg showed downregulation in retinal malondialdehyde, NLRP3 and interlukin-1β levels; improvements in the retinal pathologies; enhanced immunostaining for BDNF and improved ultra-structures in different retinal layers. Overall, the current results suggest topiramate as a neuroprotective agent for DREN, and future studies are warranted to further elucidate the mechanism of its protective action. |
