1. Protective effect of metformin on rat diabetic retinopathy involves suppression of toll-like receptor 4/nuclear factor-k B expression and glutamate excitotoxicity.
- Author
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Alomar SY, M Barakat B, Eldosoky M, Atef H, Mohamed AS, Elhawary R, El-Shafey M, Youssef AM, Elkazaz AY, Gabr AM, Elaskary AA, Salih MAK, Alolayan SO, and Zaitone SA
- Subjects
- Animals, Diabetes Mellitus, Experimental chemically induced, Diabetes Mellitus, Experimental metabolism, Diabetic Retinopathy etiology, Diabetic Retinopathy metabolism, Diabetic Retinopathy pathology, Male, NF-kappa B genetics, Oxidative Stress drug effects, Rats, Wistar, Retina metabolism, Retina pathology, Signal Transduction, Streptozocin, Toll-Like Receptor 4 genetics, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, Vascular Endothelial Growth Factor A metabolism, Rats, Diabetes Mellitus, Experimental drug therapy, Diabetic Retinopathy prevention & control, Glutamic Acid metabolism, Hypoglycemic Agents pharmacology, Metformin pharmacology, NF-kappa B metabolism, Retina drug effects, Toll-Like Receptor 4 metabolism
- Abstract
Microvascular complications of diabetes mellitus are progressively significant reasons for mortality. Metformin (MET) is considered as the first-line therapy for type 2 diabetes patients, and may be especially beneficial in cases of diabetic retinopathy although the precise mechanisms of MET action are not fully elucidated. The current study was designed to inspect the antioxidant and modulatory actions of MET on DRET in streptozotocin-induced diabetic rats. The effect of MET on the toll-like receptor 4/nuclear factor kappa B (TLR4/NFkB), inflammatory burden and glutamate excitotoxicity was assessed. Twenty-four male rats were assigned to four experimental groups: (1) Vehicle group, (2) Diabetic control: developed diabetes by injection of streptozotocin (60 mg/kg, i.p.). (3&4) Diabetic + MET group: diabetic rats were left for 9 weeks without treatment and then received oral MET 100 and 200 mg/kg for 6 weeks. Retinal samples were utilized in biochemical, histological, immunohistochemical and electron microscopic studies. MET administration significantly decreased retinal level of insulin growth factor and significantly suppressed the diabetic induced increase of malondialdehyde, glutamate, tumor necrosis factor-α and vascular endothelial growth factor (VEGF). Further, MET decreased the retinal mRNA expression of NFkB, tumor necrosis factor-α and TLR4 in diabetic rats. The current findings shed the light on MET's efficacy as an adjuvant therapy to hinder the development of diabetic retinopathy, at least partly, via inhibition of oxidative stress-induced NFkB/TLR4 pathway and suppression of glutamate excitotoxicity., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2021
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