Publications by authors named "Rehab E Abo El Gheit"

10 Publications

  • Page 1 of 1

Unraveling the biomechanistic role of Rac1/TWEAK/Fn14/NF-κB intricate network in experimentally doxorubicin-induced cardiotoxicity in rats: The role of curcumin.

J Biochem Mol Toxicol 2021 May 28:e22829. Epub 2021 May 28.

Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt.

Doxorubicin (DOX) is an important chemotherapeutic drug. Cardiotoxicity diminishes its clinical efficacy. We aimed to focus on the mechanism of DOX-induced cardiotoxicity, in addition, to evaluate curcumin's protective effect against it. Twenty-eight rats were divided into the normal control group I, curcumin-treated (200 mg/kg body weight [b.w.]) group II, DOX-treated (4 mg/kg b.w.) group III, and DOX + curcumin group IV. Cardiac injury markers, heart tissue oxidative stress indices, interferon-gamma (INF-γ), tumor necrosis factor-like weak inducer of apoptosis (TWEAK), upregulated modulator of apoptosis (PUMA), p53 and nuclear factor kappa-B p65 (NF-κB p65) levels as well as messenger RNA gene expression of Rac1 and fibroblast growth factor-inducible protein 14 (Fn14) were assayed, besides the assay of DNA damage, histopathological changes, survivin immunohistochemistry and electron microscopic examination. Curcumin significantly downregulated Rac1 and Fn14 gene expression and significantly decreased p53, NF-κB p65, INF-γ, and PUMA levels in the cardiac tissue. In addition, curcumin improved oxidative stress indices, DNA damage, and cardiac toxicity markers in the form of lactate dehydrogenase (LD), creatine kinase isoenzyme-MB (CK-MB), and cardiac troponin-I (cTn-I). Meanwhile, upregulated antiapoptotic marker survivin was observed. Light and electron microscopic findings confirmed our biochemical and molecular outcomes. The current study established the antioxidant, anti-inflammatory, and antiapoptotic roles of curcumin against DOX cardiotoxicity.
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http://dx.doi.org/10.1002/jbt.22829DOI Listing
May 2021

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

Retinoprotective effect of agmatine in streptozotocin-induced diabetic rat model: avenues for vascular and neuronal protection : Agmatine in diabetic retinopathy.

J Physiol Biochem 2021 May 26;77(2):305-320. Epub 2021 Feb 26.

Physiology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.

Diabetic retinopathy (DR) is the most common diabetic neurovascular complication, and the leading cause of preventable blindness among working-age individuals. Recently, agmatine, the endogenous decarboxylated L-arginine, has gained attention as a pleiotropic agent that modulates the diabetes-associated decline in quality of life, and exhibited varied protective biological effects. Diabetes was induced by a single streptozotocin (STZ, 50 mg/kg, i.p.) injection. When diabetes was verified, the animals were randomly allocated into three groups (16 rat each); diabetic, agmatine-treated diabetic (1 mg/kg, daily, for 12 weeks), and control group. Blood glucose homeostasis, retinal redox status, apoptotic parameters, nitric oxide synthase (NOS), nitric oxide (NO), vascular endothelial growth factor (VEGF), glutamate, glutamine, glutamine synthase (GS) activity, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and mitogen-activated protein kinase (MAPKs) pathways were assayed biochemically. Retinal vascular permeability was measured. Retinal morphology was evaluated by hematoxylin and eosin staining. Retinal N-methyl-D-aspartic acid receptor1 (NMDAR1) and glutamate aspartate transporter (GLAST) mRNA were quantified. Glucose transporter 1, pro-caspase3, and glial fibrillary acidic protein (GFAP) expression were quantified by immunohistochemistry. Chronic agmatine treatment abrogated STZ-induced retinal neurodegeneration features including gliosis, and neuronal apoptosis, restored retinal vascular permeability, mostly through antioxidant, anti-apoptotic capacity, abolishing glutamate excitotoxicity, modulating the activity of NMDARs, MAPKs/NFκB, and NOS/NO pathways. By restoring the molecular and functional background of retinal neurovascular homeostatic balance, agmatine would be appropriate therapeutic option acting upstream of the DR, impeding its progression.
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http://dx.doi.org/10.1007/s13105-021-00799-9DOI Listing
May 2021

Effect of spexin on renal dysfunction in experimentally obese rats: potential mitigating mechanisms via galanin receptor-2.

Arch Physiol Biochem 2021 Feb 25:1-10. Epub 2021 Feb 25.

Department of Physiology, Tanta University, Tanta, Egypt.

This study declared effect of spexin (SPX) on renal dysfunction in obese rats and its potential mitigating mechanisms which could mediated via galanin receptor-2 (GALR-2). Thirty two 32 Wistar male rats were arranged into four groups: control, high fat/fructose diet (HFFD), HFFD + SPX and HFFD + M871 (galanin receptor 2 antagonist)+SPX. At the termination of the experiment, urine volume, body mass index, Lee index and mean arterial blood pressure were assessed. Renal function was evaluated. Lipid profile, fasting glucose, insulin, insulin resistance and SPX levels were estimated. Also, renal histopathological, immunohistochemical and relative gene expression of renal tissue were done. Also, renal protein carbonyl, reduced glutathione, interferon gamma, monocyte chemoattractant protein-1, interleukin-10 and hydroxyproline were determined.Our results explored that SPX treatment prominently mitigated the metabolic changes and renal dysfunction induced by HFFD via GALR-2. SPX improved insulin resistance, dyslipidemia, renal oxidative stress, inflammation, apoptosis, and fibrosis. So, SPX can be considered as prospective therapeutic agent for treating renal dysfunction.
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http://dx.doi.org/10.1080/13813455.2021.1887265DOI Listing
February 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

Unique Novel Role of Adropin in a Gastric Ulcer in a Rotenone-Induced Rat Model of Parkinson's Disease.

ACS Chem Neurosci 2020 10 23;11(19):3077-3088. Epub 2020 Sep 23.

Physiology Department, Faculty of Medicine, Tanta University, Tanta 31511, Egypt.

Parkinson's disease (PD) is the second most common neurodegenerative disease, frequently associated with a gastric ulcer. We aimed to investigate the adropin neuroprotective/gastroprotective potential in the indomethacin (IND)-induced gastric ulcer in a rotenone-induced PD model. Rats were randomly divided into four groups: normal control group, rotenone/IND treated (PD /Ulcer) group, adropin treated PD/Ulcer group, and l-dopa/omeprazole (Om) treated PD/Ulcer group. There were ten rats selected for the normal control group. Striatal dopamine (DA), apoptosis/redox status, and motor/behavioral impairments were evaluated. Gastric oxidative stress, H/K-ATPase activity, prostaglandin E2, mucin content, and von Willebrand factor were measured. Gastric/striatal phosphatidylinositol 3-kinase (PI3K)/phosphorylated Akt and gastric vascular endothelial growth factor (VEGF)/striatal P53 immunoreactivities were checked. Striatal ()/ () expressions were evaluated. Adropin successfully restored striatal DA and attenuated rotenone-induced motor/behavior deficits along with strong gastroprotective potential, possibly through antioxidant activity via reduction in malondialdehyde level and upregulated superoxide dismutase, catalase activities, and serum ferric reducing antioxidant power. Adropin restored the delicate balance between the defective pro-survival PI3K/Akt/murine double minute 2 signals and apoptotic P53/ pathways. Adropin can be considered as a uniquely attractive therapeutic target in PD and its associated gastric ulcer.
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http://dx.doi.org/10.1021/acschemneuro.0c00424DOI Listing
October 2020

Role of serine protease inhibitor, ulinastatin, in rat model of hepatic encephalopathy: aquaporin 4 molecular targeting and therapeutic implication.

J Physiol Biochem 2020 Nov 14;76(4):573-586. Epub 2020 Aug 14.

Physiology Department, Faculty of Medicine, Tanta University, El Geesh Street, Tanta, Egypt.

Hepatic encephalopathy (HE) is a devastating neuropsychiatric presentation of the advanced hepatic insufficiency. It is associated with high morbidity and mortality. Aquaporin-4 (AQP4), the principal astrocyte water channel, is primarily involved in brain edema development. Ulinastatin (ULI) is a potent protease inhibitor, extracted from fresh human urine. We hypothesized that ULI could be neuroprotective in acute HE through molecular targeting of brain AQP4, which is known to be upregulated in HE. To induce acute liver failure (ALF), the rats were acutely intoxicated with thioacetamide (TAA). Animals were randomized into HE- and ULI-treated HE groups, with control normal group. Total bilirubin, albumin, serum aminotransferases, and serum/brain ammonia/proinflammatory cytokines, blood-brain barrier (BBB) integrity/tight junction proteins, brain water content, and neurological scores were assessed. Additionally, brain AQP4 and α-Syntrophin mRNA expression and protein levels were evaluated by quantitative real-time PCR and enzyme-linked immunosorbent assay, respectively. Brain and liver tissues were stripped and processed for further microscopic and histological analyses. ULI exerted potent dual neuro/hepato protective potential, improved neurological score, animals' survival, ameliorated brain edema, probably via anti-inflammatory activity, preserved BBB integrity, down-regulated AQP4 expression, and membrane polarization by decreased α-syntrophin level, with rescued brain bioenergetics. ULI could be tooled as a possible therapeutic option in HE in ALF.Graphical abstract The possible ULI mediated protection in TAA-induced HE rat model.
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http://dx.doi.org/10.1007/s13105-020-00762-0DOI Listing
November 2020

Assessment of two novel renal tubular proteins in type 2 diabetic patients with nephropathy.

J Investig Med 2020 03 12;68(3):748-755. Epub 2019 Nov 12.

Medical Biochemistry, Tanta University Faculty of Medicine, Tanta, Egypt.

Nephropathy is a common health issue associated with type 2 diabetes mellitus (T2DM). Treatment of diabetic nephropathy (DN) in an early stage can effectively inhibit its progression. Albuminuria is the currently accepted marker for detection of DN.This study aims to evaluate the urinary level of two novel renal tubular proteins (cyclophilin A and periostin) in patients with T2DM and among different nephropathy stages and also to validate the diagnostic accuracy of both cyclophilin A and periostin as potential markers for early prediction of DN relative to albuminuria.This cross-sectional study recruited 137 patients with T2DM, and they were divided based on their urinary albumin:creatinine ratio into T2DM with normoalbuminuria (), incipient T2DN with microalbuminuria () and overt T2DN with macroalbuminuria ( ) beside 41 healthy subjects as Cyclophilin A and periostin were measured in the urine using ELISA. Diagnostic accuracy of both markers was determined for prediction of DN via receiver operating characteristic curve analyses.Urinary cyclophilin A and periostin levels were significantly higher in DN groups when compared with T2DM with normoalbuminuria group. For prediction of incipient and overt DN, areas under the curve (AUCs) of periostin were 0.954, 0.997 and cyclophilin A were 0.914, 0.937, respectively. AUCs of periostin were higher than that for cyclophilin A with a significant AUC difference (p=0.022) in overt DN stage.Periostin and cyclophilin A could be regarded as a potential urinary biomarker for early prediction of DN. Periostin exhibits a higher diagnostic accuracy than urinary cyclophilin A specifically in overt DN stage.
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http://dx.doi.org/10.1136/jim-2019-001135DOI Listing
March 2020

Targeting ERK/COX-2 signaling pathway in permethrin-induced testicular toxicity: a possible modulating effect of matrine.

Mol Biol Rep 2020 Jan 16;47(1):247-259. Epub 2019 Oct 16.

Pharmacology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.

Permethrin (PER), the prevalent synthetic pyrethroid, was reported to have genotoxic effects along with male reproductive organs impairment. Matrine, the Chinese herb chief alkaloid constituent, is used extensively owing to its recognized pharmacological properties. The study included 30 rats allocated equally into three groups; Group I: Control group, Group II: PER group and Group III: Matrine treated PER group. All groups were subjected to the measurement of Steroidogenic acute regulatory (StAR) gene expression by PCR technique while testosterone, phosphorylated Extracellular signal-regulated Kinase 1/2 (p-ERK1/2) and Cyclooxygenase 2 (COX-2) levels were assessed by ELISA technique. Malondialdehyde (MDA), total antioxidant capacity (TAC) and glutathione peroxidase (GPx) were also detected spectrophotometrically in addition to assessment of DNA fragmentation. Testicular histological structure as well as sperm count and morphology were studied. Matrine improved testicular toxicity evidenced by significant upregulation of StAR gene expression, elevation of testosterone level and significant decrease of p-ERK1/2 and COX-2 levels. Moreover, enhancements of the antioxidant status together with improvement of the histological findings were observed. These findings could pave the way for matrine to be used as a promising therapeutic agent in treatment of PER toxicity.
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http://dx.doi.org/10.1007/s11033-019-05125-7DOI Listing
January 2020

Therapeutic potential of sodium selenite in letrozole induced polycystic ovary syndrome rat model: Targeting mitochondrial approach (selenium in PCOS).

Arch Biochem Biophys 2019 08 25;671:245-254. Epub 2019 Jun 25.

Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt.

Polycystic ovary syndrome (PCOS) is the most common endorinopathy in fertile women with heterogeneous reproductive and metabolic phenotypes and unknown etiology. This study was undertaken to investigate the beneficial effect of selenium in management of letrozole induced PCOS and its role in modulating mitochondrial dynamics, and its associated signals. Twenty four adult female rats were enrolled and randomly divided into four equal groups; control group received 0.5% w/v carboxymethyl cellulose (CMC); PCOS group received letrozole (1 mg/kg, daily) in 0.5% CMC for 21 days. From day 22 to day 36, after letrozole PCOS induction, the (PCOS +Metformin) group received metformin (2 mg/kg, daily) while (PCOS + sodium selenite) group received sodium selenite (0.1 mg/kg, daily). All doses were given via oral gavage. At the study end, serum hormone levels, lipid profile and HOMA-IR were assessed. Ovaries were dissected, used for histopathological evaluation, immunohistochemical detection of B-cell lymphoma-2 (Bcl-2), and its associated X protein (Bax) expression, measurement of redox status, mitochondrial dynamics markers and citrate synthase (CS) activity. Furthermore Mitofusins 2 (Mfn2) and dynamin related protein 1 (Drp1) mRNA expression was assessed by real time PCR. Selenium treatment of PCOS rats succeeded, comparable to metformin, to greatly improve the PCOS associated endocrine and metabolic phenotypes and histopathological changes, mostly through modulating mitochondrial dynamics, anti-apoptotic action, alleviating oxidative stress and mitochondrial dysfunction. So, selenium could provide a novel therapeutic strategy for PCOS.
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http://dx.doi.org/10.1016/j.abb.2019.06.009DOI Listing
August 2019
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