Publications by authors named "Amany Y Elkazaz"

5 Publications

  • Page 1 of 1

Novel Mechanism for Memantine in Attenuating Diabetic Neuropathic Pain in Mice via Downregulating the Spinal HMGB1/TRL4/NF-kB Inflammatory Axis.

Pharmaceuticals (Basel) 2021 Apr 1;14(4). Epub 2021 Apr 1.

Department of Pharmacology & Toxicology, Faculty of Pharmacy, Sinai University, El-Arish, North Sinai 45511, Egypt.

Diabetic neuropathic pain (DNP) is a common diabetic complication that currently lacks an efficient therapy. The aim of the current work was to uncover the anti-allodynic and neuroprotective effects of memantine in a model of mouse diabetic neuropathy and its ameliorative effect on the high-mobility group box-1 (HMGB1)/toll-like receptor 4 (TLR4)/nuclear factor-k B (NF-kB) inflammatory axis. Diabetes was prompted by an alloxan injection (180 mg/kg) to albino mice. On the ninth week after diabetes induction, DNP was confirmed. Diabetic mice were randomly allocated to two groups (six mice each); a diabetes mellitus (DM) group and DM+memantine group (10 mg/kg, daily) for five weeks. DNP-related behaviors were assessed in terms of thermal hyperalgesia and mechanical allodynia by hot-plate and von Frey filaments. Enzyme-linked immunosorbent assay (ELISA) kits were used to measure the spinal glutamate, interleukin-1 beta (IL-1β), and tumor necrosis factor-α (TNF-α). The spinal levels of N-methyl-D-aspartate type 1 receptor (NMDAR1), HMGB1, TLR4, and phosphorylated NF-kB were assessed using Western blotting. Histopathological investigation of the spinal cord and sciatic nerves, together with the spinal cord ultrastructure, was employed for assessment of the neuroprotective effect. Memantine alleviated pain indicators in diabetic mice and suppressed excessive NMDAR1 activation, glutamate, and pro-inflammatory cytokine release in the spinal cord. The current study validated the ability of memantine to combat the HMGB1/TLR4/NF-kB axis and modulate overactive glutamate spinal transmission, corroborating memantine as an appealing therapeutic target in DNP.
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http://dx.doi.org/10.3390/ph14040307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065430PMC
April 2021

Protective effect of metformin on rat diabetic retinopathy involves suppression of toll-like receptor 4/nuclear factor-k B expression and glutamate excitotoxicity.

Int Immunopharmacol 2021 Jan 25;90:107193. Epub 2020 Nov 25.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia. Electronic address:

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.
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http://dx.doi.org/10.1016/j.intimp.2020.107193DOI Listing
January 2021

Carbamazepine Alleviates Retinal and Optic Nerve Neural Degeneration in Diabetic Mice via Nerve Growth Factor-Induced PI3K/Akt/mTOR Activation.

Front Neurosci 2019 1;13:1089. Epub 2019 Nov 1.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.

Diabetic retinopathy causes loss of vision in adults at working-age. Few therapeutic options are available for treatment of diabetic retinopathy. Carbamazepine (CARB), a widely used antiepileptic drug, was recently accounted for its neuroprotective effect. Nerve growth factor (NGF) activates various cascades among which, PI3K/Akt/mTOR pathway has a vital action in NGF-mediated neuronal differentiation and survival. This study evaluated the effect of CARB in the treatment of diabetic retina and unveiled some of the underlying molecular mechanisms. Alloxan diabetes model was induced in 36 albino well-acclimatized mice. After establishment of the diabetic model in 9 weeks, mice were assigned to treatment groups: (1) saline, (2) alloxan-diabetic, (3 and 4) alloxan+CARB (25 or 50 mg per kg p.o) for 4 weeks. After completion of the therapeutic period, mice were sacrificed and eyeballs were enucleated. Retinal levels of NGF and PI3K/Akt were assessed using real-time polymerase chain reaction. Further, total and phosphorylated TrKA, PI3K, Akt, mTOR as well as Caspase-3 were measured by Western blot analysis. Histopathological examination demonstrated that CARB attenuated vacuolization and restored normal thickness and organization of retinal cell layers. In addition, CARB increased pTrKA/TrKA ratio and ameliorated diabetes-induced reduction of NGF mRNA and immunostaining in retina. Additionally, it augmented the mRNA expression of PI3K and Akt, as well as the protein level of the phosphorylated PI3/Akt/mTOR. Results highlighted, for the first time, the neuronal protective effect for CARB in diabetic retina, which is mediated, at least in part, by activation of the NGF/PI3K/Akt/mTOR pathway.
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http://dx.doi.org/10.3389/fnins.2019.01089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838003PMC
November 2019

Anti-inflammatory and neuroprotective activity of boswellic acids in rotenone parkinsonian rats.

Can J Physiol Pharmacol 2017 Jul 1;95(7):819-829. Epub 2017 Mar 1.

d Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.

There is evidence that inflammation and oxidative stress contribute to the neurodegenerative changes observed in Parkinson's disease. Unfortunately, there is a lack of curative treatment for this debilitating movement disorder. Boswellic acids (BAs) are pentacyclic triterpene molecules of plant origin that have been utilized for treating many inflammatory conditions. The current study was conducted to explore the protective role of BAs against rotenone-induced experimental parkinsonism. Twenty-four rats were assigned to one of four treatment groups. The first two groups were a vehicle group (no rotenone) and a rotenone control group in which rats received rotenone (1 mg/kg) every 48 h. The next 2 groups received rotenone (1 mg/kg every 48 h) plus protective oral doses of BAs (125 or 250 mg/kg daily). Rats in the rotenone group showed motor dysfunction when tested in the open-field arena and cylinder and rotarod tests. Moreover, inflammatory markers increased, whereas the dopamine level was lower in the striata of rats in the rotenone group versus those in the vehicle group. BAs taken by rats with rotenone-induced parkinsonism showed enhanced general motor performance, reduced inflammatory markers, and increased striatal dopamine level and nigral tyrosine hydroxylase immunostaining. In conclusion, BAs are promising agents in slowing the progression of Parkinson's disease if appropriate data become available about their safety and efficacy in humans.
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http://dx.doi.org/10.1139/cjpp-2016-0158DOI Listing
July 2017

The effect of oral contraceptive different patterns of use on circulating IGF-1 and bone mineral density in healthy premenopausal women.

Endocrine 2015 Feb 27;48(1):272-8. Epub 2014 May 27.

Department of Medical Biochemistry, Faculty of Medicine, Suez Canal University, Ismailia, Egypt,

Both insulin-like growth factor-1(IGF-1) and oral contraceptive (OC) use have been linked to premenopausal breast and colorectal cancers, osteoporosis and cardiovascular disease. Understanding the effects of different patterns of use of OC on IGF-1 levels and bone mineral density (BMD) may offer insight into its influence on osteoporosis. We conducted a cross-sectional study, which included 135 women, who were then divided into three groups: Group A who were OC current users, 41 women; Group B who never use OC, 51 women; and Group C who were past users of OC, 41 women. Each patient completed a questionnaire on demographic parameters, marital state history and contraception history including duration of use and type of contraceptive pills or used method. Lower-end radius, proximal femur and lumbar spine BMD were measured by dual-energy X-ray absorptiometry. IGF-1 was assessed with chemiluminescent immunometric assay. The three groups were similar in total body T value of BMD (with slight better results in past users than the other two groups but it was statistically insignificant difference), and past users showed significantly higher BMD values compared to current users at spine, femur and forearm. Nonusers also had better BMD values compared to current users (spine and forearm BMD). Among past users, the mean level of circulating IGF-1 was higher than the other two groups and that difference was statistically significant. Past OC use and/or nonuse has a more favorable impact on BMD compared to current use and that this relationship is in part mediated by IGF-1. Hence, it appears that OC use is beneficial to BMD if used in the past and then discontinued or if never used at all compared to current use.
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http://dx.doi.org/10.1007/s12020-014-0290-2DOI Listing
February 2015
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