Memantine mitigates ROS/TXNIP/NLRP3 signaling and protects against mouse diabetic retinopathy: Histopathologic, ultrastructural and bioinformatic studies.

Autor: ElSayed MH; Department of Physiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt. Electronic address: Doctorpioneer@med.asu.edu.eg., Elbayoumi KS; Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; Department of Basic medical Sciences, Ibn Sina University for Medical Sciences, Amman 16197, Jordan., Eladl MA; Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates., Mohamed AAK; Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt., Hegazy A; Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt., El-Sherbeeny NA; Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt., Attia MA; Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; Department of Basic medical sciences, College of Medicine, AlMaarefa University, 71666, Riyadh 11597, Saudi Arabia., Hisham FA; Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt., Saleh MAK; Ophthalmology Department, Al-Asher Asyut Faculty of Medicine for Men, Asyut, Egypt., Elaskary A; Ophthalmology Department, Al-Asher Asyut Faculty of Medicine for Men, Asyut, Egypt., Morsi K; Department of Anesthesia Technology, College of Applied Medical Sciences in Jubail, Imam Abdulrahman Bin Faisal University, Jubail 35811, Saudi Arabia. Electronic address: kmibraheem@iau.edu.sa., Mustsafa AMA; Department of Pediatric Nursing, Jazan University, Jazan 45142, Saudi Arabia., Enan ET; Department of Basic medical sciences, College of Medicine, AlMaarefa University, 71666, Riyadh 11597, Saudi Arabia; Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt., Zaitone SA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt. Electronic address: Szaitone@ut.edu.sa.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2023 Jul; Vol. 163, pp. 114772. Date of Electronic Publication: 2023 Apr 26.
DOI: 10.1016/j.biopha.2023.114772
Abstrakt: Diabetic retinopathy (DRET) triggers vision loss in adults, however, little therapeutic options are existing. Memantine is an anti-Alzheimer drug that antagonizes the activity of glutamate at N-methyl-D-aspartate (NMDA) receptors. Glutamate and thioredoxin-interacting protein (TXNIP) are known to be overexpressed in diabetic retinas and can produce activation of NOD-like receptor protein 3 (NLRP3) with subsequent secretion of interlukin-1β. This study repurposed memantine for its neuroprotective effect in experimental DRET and tested its impact on ROS/TXNIP/NLRP3. In addition, KEGG pathway database and STRING database identified the protein-protein interaction between glutamate receptors and TXNIP/NLRP3. Male Swiss albino mice received alloxan (180 mg/kg) to induce DRET. After 9 weeks, we divided the mice into groups: (a) saline, (ii) DRET, (iii and iv) DRET + oral memantine (5 or 10 mg per kg) for 28 days. Then, mice were euthanized, and eyeballs were removed. Retinal samples were utilized for biochemical, histopathological, and electron microscopy studies. Retinal levels of glutamate, TXNIP, NLRP3 and interlukin-1β were estimated using ELISA technique as well as retinal malondialdehyde. Histopathological and ultrastructural examination demonstrated that oral memantine attenuated vacuolization and restored normal retinal cell layers. Moreover, memantine reduced TXNIP, NLRP3, interleukin-1β and MDA concentrations. These results provide evidence demonstrating memantine' efficacy in alleviating DRET via suppressing reactive oxygen species/TXNIP/NLRP3 signaling cascade. Therefore, memantine might serve as a potential therapy for retinopathy after adequate clinical research.
Competing Interests: Conflict of interest statement Authors of article titled (Memantine mitigates ROS/TXNIP/NLRP3 signaling and protects against mouse diabetic retinopathy: experimental and bioinformatic studies) declares they have no potential conflicts of interests.
(Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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