Publications by authors named "Rehab M El-Sayed"

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

Vincamine protects against cisplatin induced nephrotoxicity via activation of Nrf2/HO-1 and hindering TLR4/ IFN-γ/CD44 cells inflammatory cascade.

Life Sci 2021 May 19;272:119224. Epub 2021 Feb 19.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University, El-Arish, Egypt.

Cisplatin is a commonly prescribed chemotherapeutic agent for the treatment of different types of solid tumors. However, the high incidence of cisplatin-induced nephrotoxicity largely restricts its clinical efficacy in absence of both preventive and treatment options to combat its serious and life-threatening effects. Therefore, the current study investigated the reno-protective molecular mechanisms of vincamine against cisplatin nephrotoxicity. Vincamine (40 mg/kg P.O.) was given for 7 days, cisplatin was injected as single dose (10 mg/kg i.p.) at the seven day of the experiments. Animals were sacrificed after 72 h of cisplatin injection to allow nephrotoxicity. Vincamine pretreatment improved kidney functions and decreased kidney function tests as urea, creatinine and kidney injury molecule-1 (KIM-1), as well as it exhibited antioxidant properties by restoring balance between pro and anti-oxidants of malondialdehyde (MDA), myeloperoxidase (MPO), nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1). Moreover, vincamine hindered the inflammatory cascade via mediating Toll like receptor 4 (TLR4)- interferon gamma (IFNγ)-CD44 cells pathway and transforming growth factor beta (TGFβ1). Additionally, vincamine retained DNA fragmentation. In conclusion, vincamine represents a promising intervention in limiting cisplatin nephrotoxicity by its anti-oxidant, anti-inflammatory, antiapoptotic mechanistic activities. Therefore, vincamine can be used as adjunct therapy with cisplatin to mitigate cisplatin-induced-AKI.
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http://dx.doi.org/10.1016/j.lfs.2021.119224DOI Listing
May 2021

Protective role of lycopene against metabolic disorders induced by chronic bisphenol A exposure in rats.

Environ Sci Pollut Res Int 2020 Mar 8;27(9):9192-9201. Epub 2020 Jan 8.

Department of Physiology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt.

This study was conducted to elucidate the ameliorative potential of lycopene (LYC) against the metabolic toxicity induced by bisphenol A (BPA) in rats. Male rats (n = 28) were divided into 4 equal groups: control group, LYC group was given lycopene (10 mg/kg BW), BPA group was given 10 mg/kg BW of BPA, and the last group was administered BPA and LYC at 10 mg/kg via gavage for 90 consecutive days. Body weight (BW) gain, lipid profile, and total antioxidant capacity (TAC) were assessed. Oral glucose tolerance test (OGTT), homeostasis model assessment-estimated insulin resistance (HOMA-IR), thyroid hormones, interleukin-1 beta (IL-1β), leptin, and resistin were assayed. Moreover, immunohistochemistry of TNF-α was performed in adipose tissue. BPA-treated rats showed significant reduction in BW gain and deteriorations in lipid profile, TAC, OGTT, and thyroid hormones as well as significant increases in HOMA-IR, IL-1β, leptin, and resistin. While, improvement of metabolic parameters was observed when LYC was administrated with BPA. Intense TNF-α immunostaining was detected in the fat of BPA-treated rats but the intensity decreased when LYC was administrated with BPA. In conclusion, LYC ameliorated the adverse effects of BPA on metabolism through its antioxidant potential and its reduction of TNF-α expression in adipose tissue.
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http://dx.doi.org/10.1007/s11356-019-07509-5DOI Listing
March 2020

Physical & mental activities enhance the neuroprotective effect of vinpocetine & coenzyme Q10 combination against Alzheimer & bone remodeling in rats.

Life Sci 2019 Jul 4;229:21-35. Epub 2019 May 4.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University, Egypt.

Background: Alzheimer's disease is a neurodegenerative disorder characterized by a progressive decline of cognitive abilities as well as bone loss. Physical and mental activities maintain cognitive functions as well as increase bone mass by inhibiting bone resorption. VIN and CoQ10 are neuroprotective drugs that possess anti-inflammatory and antioxidant properties.

Aims: To study the effect of PH&M on enhancing the neuroprotective role of VIN and CoQ10 combination during induction of AD model in rats besides their role against bone mass loss associated with AD model.

Main Methods: Six groups of rats were received saline, AlCl, and PH&M daily either alone or with a combination of VIN and CoQ10 for 4 weeks. Various biochemical analyses were performed to evaluate the extent of brain damage such as ACHE, β-secretase, chitinase, Aβ, tau protein, and monoamines besides the inflammatory and antioxidant parameters. Serum levels of minerals as well as 25-OHD, PTH, RANKL, and OPG levels were measured to detect the extent of bone impairment. Also, histopathological changes were evaluated in different brain regions and hind paw.

Key Findings: VIN and CoQ10 combination together with PH&M significantly attenuated the neurodegeneration induced by AlCl administration through the improvement of AD markers in brain tissue as well as oxidant and inflammatory markers. Bone resorption markers, serum minerals, and PTH levels were also normalized too.

Significance: Neuroprotective drugs together with PH&M have a more protective effect against AD and bone loss rather than PH&M alone.
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http://dx.doi.org/10.1016/j.lfs.2019.05.006DOI Listing
July 2019

Apoptosis perturbations and expression of regulatory inflammatory factors in cisplatin-depleted rat livers under l-arginine protection.

Can J Physiol Pharmacol 2019 May 27;97(5):359-369. Epub 2019 Mar 27.

b Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.

Hepatic injury is one of the most common complications associated with cisplatin (CIS) use. Recently, liver protection lines are being discovered to stop the hepatic cell death due to inflammatory and apoptotic perturbations. l-arginine has protective effects in several models of liver injury. This study was designed to investigate the possible protective effect of l-arginine against CIS-induced acute hepatic injury in rats. Rats were divided into 4 groups: control, l-arginine, CIS, l-arginine + CIS. Liver function, oxidative stress, inflammatory cytokines, and apoptosis markers were assessed. l-arginine pretreatment protected the liver against CIS-induced toxicity as indicated by significantly alleviating the changes in liver function along with restoration of the antioxidant status. This finding was confirmed with the markedly improved pathological changes. l-arginine showed anti-inflammatory effect through the reduction of liver expression of iNOS, TNF-α, and NF-κβ, which were ameliorated to significant levels. Furthermore, l-arginine administration downregulated the liver expression of the apoptotic marker, caspase-3. The results recommend l-arginine as a hepatoprotective agent against CIS toxicity. Mostly, this hepatoprotective effect of l-arginine involved anti-inflammatory and anti-apoptotic activities.
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http://dx.doi.org/10.1139/cjpp-2018-0706DOI Listing
May 2019
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