Publications by authors named "Sahar S Abd El-Rahman"

18 Publications

  • Page 1 of 1

Evaluation of the Ameliorative Effect of Zinc Nanoparticles against Silver Nanoparticle-Induced Toxicity in Liver and Kidney of Rats.

Biol Trace Elem Res 2021 Apr 14. Epub 2021 Apr 14.

Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

Silver nanoparticles (Ag-NPs) have various pharmaceutical and biomedical applications owing to their unique physicochemical properties. Zinc (Zn) is an essential trace element, a strong antioxidant, and has a primary role in gene expression, enzymatic reactions, and protein synthesis. The present study aims to explore the toxic effects of Ag-NPs (50 nm) on the liver and kidney of rats and also to evaluate the potential protective effect of Zn-NPs (100 nm) against these adverse effects. Forty adult Sprague-Dawley rats were randomly divided into four equal groups: control group, Ag-NPs group, Zn-NPs group, and Ag-NPs + Zn-NPs group. Ag-NPs (50 mg/kg) and/or Zn-NPs (30 mg/kg) were administered daily by gavage for 90 days. The results showed that exposure to Ag-NPs increased serum ALT, AST, urea, and creatinine. Ag-NPs also induced oxidative stress and lipid peroxidation and increased inflammatory cytokines in hepatic and renal tissues. Moreover, histopathological and immunohistochemical examinations revealed various histological alterations and positive caspase-3 expressions in the liver and kidney following exposure to Ag-NPs. On the other hand, most of these toxic effects were ameliorated by co-administration of Zn-NPs. It was concluded that Ag-NPs have hepatotoxic and nephrotoxic effects in rats via different mechanisms including oxidative stress, inflammation, and apoptosis and that Zn-NPs can be used to alleviate these harmful effects by their antioxidative, anti-inflammatory, and antiapoptotic properties.
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http://dx.doi.org/10.1007/s12011-021-02713-2DOI Listing
April 2021

Zinc Nanoparticles Ameliorate the Reproductive Toxicity Induced by Silver Nanoparticles in Male Rats.

Int J Nanomedicine 2021 31;16:2555-2568. Epub 2021 Mar 31.

Department of Toxicology and Forensic Medicine, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

Introduction: Silver nanoparticles (Ag-NPs) are among the most commonly used nanoparticles in different fields. Zinc nanoparticles (Zn-NPs) are known for their antioxidant effect. This study was designed to investigate the adverse effects of Ag-NPs (50 nm) on the male reproductive system and also the ameliorative effect of Zn-NPs (100 nm) against these harmful effects.

Methods: Forty adult male rats were used in this study; they were randomly divided into four equal groups: control group, Ag-NPs group, Zn-NPs group, Ag-NPs + Zn-NPs group. Ag-NPs (50 mg/kg) and/or Zn-NPs (30 mg/kg) were administered orally for 90 days.

Results: The results revealed that exposure to Ag-NPs adversely affected sperm motility, morphology, viability, and concentration. Ag-NPs also induced oxidative stress and lipid peroxidation in testicular tissue. The exposure to Ag-NPs decreased serum FSH, LH, and testosterone hormones. Additionally, comet assay revealed DNA degeneration in the testicular tissue of rats exposed to Ag-NPs. Histopathological examination showed various histological alterations in the testes of rats intoxicated with Ag-NPs. Furthermore, co-administration of Zn-NPs ameliorated most of the toxic effects of Ag-NPs via their antioxidative capacity.
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http://dx.doi.org/10.2147/IJN.S307189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020588PMC
April 2021

Poly(ADP-Ribose) Polymerase 1 Promotes Inflammation and Fibrosis in a Mouse Model of Chronic Pancreatitis.

Int J Mol Sci 2021 Mar 30;22(7). Epub 2021 Mar 30.

Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.

Chronic pancreatitis (CP) is an inflammatory disease of the pancreas characterized by ductal obstructions, tissue fibrosis, atrophy and exocrine and endocrine pancreatic insufficiency. However, our understanding is very limited concerning the disease's progression from a single acute inflammation, via recurrent acute pancreatitis (AP) and early CP, to the late stage CP. Poly(ADP-ribose) polymerase 1 (PARP1) is a DNA damage sensor enzyme activated mostly by oxidative DNA damage. As a co-activator of inflammatory transcription factors, PARP1 is a central mediator of the inflammatory response and it has also been implicated in acute pancreatitis. Here, we set out to investigate whether PARP1 contributed to the pathogenesis of CP. We found that the clinically used PARP inhibitor olaparib (OLA) had protective effects in a murine model of CP induced by multiple cerulein injections. OLA reduced pancreas atrophy and expression of the inflammatory mediators TNFα and interleukin-6 (IL-6), both in the pancreas and in the lungs. Moreover, there was significantly less fibrosis (Masson's trichrome staining) in the pancreatic sections of OLA-treated mice compared to the cerulein-only group. mRNA expression of the fibrosis markers TGFβ, smooth muscle actin (SMA), and collagen-1 were markedly reduced by OLA. CP was also induced in PARP1 knockout (KO) mice and their wild-type (WT) counterparts. Inflammation and fibrosis markers showed lower expression in the KO compared to the WT mice. Moreover, reduced granulocyte infiltration (tissue myeloperoxidase activity) and a lower elevation of serum amylase and lipase activity could also be detected in the KO mice. Furthermore, primary acinar cells isolated from KO mice were also protected from cerulein-induced toxicity compared to WT cells. In summary, our data suggest that PARP inhibitors may be promising candidates for repurposing to treat not only acute but chronic pancreatitis as well.
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http://dx.doi.org/10.3390/ijms22073593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037143PMC
March 2021

(Forssk.) Poir. (); phenolic constituents of the aqueous leaves extract and evaluation of its anti-inflammatory, analgesic activities.

Heliyon 2021 Feb 13;7(2):e06205. Epub 2021 Feb 13.

Department of Pharmacology, Medical Research Division, National Research Centre, Giza, Egypt.

Background: The plant kingdom is considered one of the most common sources for structural and biological diversity. In particular, the wild category acquires our attention to investigate the phytochemical and the biological evaluations.

Methods: was exposed to phytochemical examination using HPLC-ESI-MS analysis. Furthermore, the anti-inflammatory activity was evaluated using carrageenan-induced rat paw edema model, whereas both the central and peripheral analgesic activities were tested via hot plate test in rats and acetic acid-induced writhing in mice, respectively.

Results: Twenty phenolic compounds of aqueous leaves extract were emphasized by liquid chromatography coupled with mass spectrometry. Moreover, exhibited both anti-inflammatory and peripheral analgesic activities. Furthermore, significantly decreased the immune expression of MMP-9, TNF-α and TGF-β1 in the hind paw of rats.

Conclusion: possess peripheral anti-nociceptive and anti-inflammatory effects in rats mediated through its anti-oxidant and anti-inflammatory activities. The activity of leaves extract might be attributed to the presence of hydroxy and keto structures.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895722PMC
February 2021

Promoted inhibition of TLR4/miR-155/ NFB p65 signaling by cannabinoid receptor 2 agonist (AM1241), aborts inflammation and progress of hepatic fibrosis induced by thioacetamide.

Chem Biol Interact 2021 Feb 24;336:109398. Epub 2021 Jan 24.

Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt. Electronic address:

The endocannabinoid system plays a pivotal role, whether it is promoting or dampening hepatic fibrosis. This study investigated the role of Cannabinoid receptor 2 (CB) activation by the synthetic analog (AM1241) on revoking the progress of liver fibrosis. Thioacetamide (TAA) was used to induce liver fibrosis in rats for three weeks followed by its concurrent administration with AM1241 at two different doses for another three weeks. Markers for liver function and oxidative stress, hepatic TNF-α, IL-1β and IL-6, qRT-PCR expression of Toll like receptor 4 (TLR4), TGF-β1, α-SMA and microRNA-155 (miR-155) genes, Western blot for protein levels of Vimentin and E-cadherin, immunohistochemical expression of NFκB p65 and histopathology of liver tissue were all investigated. AM1241 administration significantly maintained liver function markers and decreased; malondialdehyde, Vimentin, TLR4, TGF-β1, α-SMA and miR-155 genes expression, NFκB p65 immune-expression and pro-inflammatory cytokines (TNF-α, IL-1β and IL-6). Additionally, AM1241 significantly increased E-Cadherin level, GSH and SOD content. Histologically, AM1241 limited fibroplasia extension, and broke the itinerary of bridging fibrosis. In conclusion, activation of the CB receptors by AM1241 promoted liver regeneration and overrun the progression of liver fibrosis through; inhibition of TLR4/miR-155/NFκB p65 pathway, suppression of pro-inflammatory IL-6, IL-1β and TNF-α, reducing TGF-β1, α-SMA, Vimentin and up-regulating E-Cadherin.
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http://dx.doi.org/10.1016/j.cbi.2021.109398DOI Listing
February 2021

Antineoplastic activity of Salmonella Typhimurium outer membrane nanovesicles.

Exp Cell Res 2021 Feb 15;399(1):112423. Epub 2020 Dec 15.

Department of Microbiology, National Research Center, Cairo, Egypt.

Nano-sized Gram-negative bacterial outer membrane vesicles possess unique structural and immunostimulatory effects that could be exploited to regress tumors by alerting the host immune system and reversing the immunosuppressive tumor microenvironment. The current study was conducted to investigate the antitumor activity of the outer membrane vesicles (ST-OMVs) of Salmonella Typhimurium ATCC 14028, in vitro in human colorectal carcinoma (HTC116), breast cancer (MCF-7), and hepatocellular carcinoma (HepG2) cell lines and in vivo in Ehrlich solid carcinoma-bearing mice model either as a mono-immunotherapy or as an adjuvant to a commonly used conventional chemotherapy. In addition, we investigated the safety of ST-OMVs. Adult Swiss albino female mice with transplanted Ehrlich solid carcinoma were treated with either ST-OMVs, paclitaxel or a combination of both. Tumor volume, growth inhibition rate, quantitative RT-PCR of Bax and VEGF genes expression, histopathology and immune-expression of caspase-3, Beclin-1, CD49b and Ki-67 were all analyzed. Our results showed that ST-OMVs significantly decreased tumor volume, significantly increased tumor growth inhibition rate, up-regulated the immunohistochemical expression of caspase-3, Beclin-1, and CD49b (enhanced recruitment of NK cells). Furthermore, ST-OMVs down-regulated the expression of Ki-67, increased Bax gene expression and decreased VEGF gene expression as detected by qRT-PCR analysis. Histologically, ST-OMVs promoted apoptosis, decreased tumor invasion and mitotic activities. Moreover, ST-OMVs showed a remarkable cytotoxic activity in various investigated in vitro cancer cell lines. Our findings demonstrate potential antitumor activity of ST-OMVs that might be used as a promising safe antitumor immunotherapy or an adjuvant to conventional chemotherapeutic drugs, resolving some of their problems.
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http://dx.doi.org/10.1016/j.yexcr.2020.112423DOI Listing
February 2021

Potential effects of ursodeoxycholic acid on accelerating cutaneous wound healing.

PLoS One 2019 23;14(12):e0226748. Epub 2019 Dec 23.

Cyclotron Project, Nuclear Research Centre, Atomic Energy Authority, Cairo, Egypt.

Among the initial responses to skin injury, triggering inflammatory mediators and modifying oxidative status provide the necessary temple for the subsequent output of a new functional barrier, fibroplasia and collagen deposition, modulated by NF-κB and TGF-β1 expressions. Hence, the current study aimed to investigate the effect of local application of ursodeoxycholic acid (UDCA) on cutaneous wound healing induced in Swiss mice. Wound contraction progression was monitored by daily photographing the wounds. Enhanced fibroblast cell migration was observed after incubation with UDCA. Topical application of UDCA (500 μM) cream on excised wounds significantly enhanced wound contraction and improved morphometric scores. In addition, UDCA ameliorated the unbalanced oxidative status of granulated skin tissues. Interestingly, it showed increased expression of TGF-β1 and MMP-2 with decreased expression of NF-κB. On the other hand, UDCA significantly increased collagen fibers deposition and hydroxyproline content and enhanced re-epithelization. UDCA also modified the mitochondrial function throughout the healing process, marked by lower consumption rates of mitochondrial ATP, complex I contents as well as intracellular NAD+ contents accompanied by elevated levels of nicotinamide compared to the untreated controls. In chronic gamma-irradiated (6Gy) model, the illustrated data showed enhanced wound contraction via increased TGF-β1/MMP-2 and collagen deposition incurred by topical application of UDCA without effect on NF-κB level. In sum, the present findings suggest that UDCA may accelerate wound healing by regulating TGF-β1 and MMP-2 and fibroplasia/collagen deposition in either the two wound healing models.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226748PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927640PMC
April 2020

Targeting AngII/AT1R signaling pathway by perindopril inhibits ongoing liver fibrosis in rat.

J Tissue Eng Regen Med 2019 12 22;13(12):2131-2141. Epub 2019 Oct 22.

Pharmacology Department, Medical Division, National Research Centre, Giza, Egypt.

The renin-angiotensin system (RAS) has a substantial role in liver fibrosis, cirrhosis, and portal hypertension. Hence, targeting RAS through angiotensin-converting enzyme (ACE) inhibitors can mend hepatic fibrosis; the current study was designed to examine the potential fibrosis inhibition activity of perindopril using a rat model of liver fibrosis induced by thioacetamide (TAA). Four groups of rats were used throughout this study, Group I (control group); rats received the vehicle. TAA was used for inducing liver fibrosis in rats by intraperitoneal injection of 200-mg/kg body weight twice a week for 6 weeks. Group II served as (TAA group). Rats of Groups III and IV were given perindopril at doses of 2 and 8 mg/kg 2 weeks after TAA administration and continued concomitantly with TAA till the end of the experiment. Injection of TAA resulted in a significant increase in aminotransferases' activities and bilirubin with a significant decrease in serum albumin and total protein and a significant decrease in hepatic content of GSH and SOD. Additionally, TAA injection raised the hepatic content of TGF-β1, α-SMA, TNF-α, and level of MDA. Histological and immunohistochemical data presented marked fibrosis in liver sections of TAA-administrated rats with increased collagen deposition, elevated METAVIR scoring, and increased expression of α-SMA, caspase-3, and AT1R. Oral dosing of perindopril for 4 weeks concomitant with TAA could mend the altered parameters near to normal values and abolished the ongoing fibrosis extension. In conclusion, these results demonstrated that perindopril, as ACE inhibitor, could grant a superior remedial nominee in preventing liver fibrosis progression through targeting angiotensin II formation.
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http://dx.doi.org/10.1002/term.2940DOI Listing
December 2019

Nanoparticles of zinc oxide defeat chlorpyrifos-induced immunotoxic effects and histopathological alterations.

Vet World 2019 22;12(3):440-448. Epub 2019 Mar 22.

Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt.

Background And Aim: Chlorpyrifos (CPF) is a widely used organophosphate insecticide. Nanoparticles of zinc oxide (ZnO NPs) physically showed effective adsorbing property for some insecticides. The study was conducted to estimate the potential effect of ZnO NPs against CPF toxicity.

Materials And Methods: Four groups of male rats were used; control group and three groups received drinking water contained 75 mg/L CPF, combined 75 mg/L CPF and 200 mg/L ZnO NPs, and 200 mg/L ZnO NPs, respectively.

Results: CPF significantly decreased macrophage activity, serum lysozyme activity, and levels of interleukin-2 (IL-2) and IL-6; increased the percentage of DNA degeneration on comet assay of lymphocytes and significantly elevated hepatic and splenic malondialdehyde contents; and decreased their glutathione contents. The liver and spleen showed marked histological alterations after exposure to CPF with decreased expression of acetylcholinesterase. The coadministration of ZnO NPs ameliorated most of the undesirable effects of CPF, through elevation of macrophage and serum lysozyme activities, increased the levels of IL-2 and IL-6, corrected the oxidative stress markers, and alleviated most of the adverse effect exerted by CPF in liver and spleen tissues.

Conclusion: The addition of ZnO NPs to CPF-contaminated drinking water may be useful as a powerful antioxidant agent against toxic damage induced by CPF particularly in individuals who are on daily occupational exposure to low doses of CPF.
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http://dx.doi.org/10.14202/vetworld.2019.440-448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487240PMC
March 2019

Does nicotine impact tramadol abuse? Insights from neurochemical and neurobehavioral changes in mice.

Neurotoxicology 2018 07 12;67:245-258. Epub 2018 Jun 12.

Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address:

Nicotine and tramadol concomitant drug dependence pose increasing social, economic as well as public threats. Accordingly, the present study investigated neurochemical, neurobehavioral and neuropathological changes in the brain subsequent to the interaction of nicotine and tramadol. To this end, tramadol (20 mg/kg, i.p) and nicotine (0.25 mg/kg, i.p) were administrated to male albino mice once daily for 30 days. Consequent to microglial activation, nicotine exacerbated oxidative/nitrosative stress induced by tramadol as manifest by the step-up in thiobarbituric acid reactive substances and nitric oxide subsequent to the enhanced levels of neuronal and inducible nitric oxide synthases; paralleled by decreased non-protein sulfhydryls. Increased oxidative stress by tramadol and/or nicotine sequentially augmented nuclear factor kappa B and the proinflammatory cytokine tumor necrosis factor α with the induction of apoptosis evident by the increased caspase-3 immunoreactivity. However, paradoxical to the boosted inflammation and apoptosis, heightened DA levels in the cortex parallel along with increased tyrosine hydroxylase in midbrain were apparent. Concomitant administration of tramadol and nicotine impaired spatial navigation in the Morris Water Maze test coupled with enhanced levels of acetyl- and butyryl cholinestrases. However, tramadol in association with nicotine improved social interaction while decreasing anxiety and aggression linked to chronic administration of nicotine, effects manifested by increased levels of serotonin and GABA. These results provide evidence that co-administration of tramadol and nicotine may enhance reward and dependence while reducing anxiety and aggression linked to nicotine administration. However, such combination exacerbated neurotoxic effects and elicited negative effects regarding learning and memory.
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http://dx.doi.org/10.1016/j.neuro.2018.06.004DOI Listing
July 2018

Mesalazine, an osteopontin inhibitor: The potential prophylactic and remedial roles in induced liver fibrosis in rats.

Chem Biol Interact 2018 Jun 5;289:109-118. Epub 2018 May 5.

Pharmacology Department, National Research Centre, Giza, Egypt.

Liver fibrosis is a major health issue leading to high morbidity and mortality. The potential anti-fibrotic activity and the effect of mesalazine on osteopontin (OPN), an extra cellular matrix (ECM) component were evaluated in TAA-induced liver fibrosis in rats. For this purpose, forty-two adult male Wistar rats were divided into six groups. All animals, except the normal control, were intraperitoneally injected with TAA (200 mg/kg) twice per week for 6 weeks. In the hepato-protective study, animals were administered mesalazine (50 and 100 mg/kg, orally) for 4 weeks before induction of liver fibrosis then concomitantly with TAA injection. In the hepato-therapeutic study, animals were administered mesalazine for 6 weeks after TAA discontinuation with the same doses. In both studies, mesalazine administration improved liver biomarkers through decreasing serum levels of AST, ALT and total bilirubin when compared to fibrotic group with significant increase in total protein and albumin levels. Mesalazine significantly decreased hepatic MDA level and counteracted the depletion of hepatic GSH content and SOD activity. Additionally, it limits the elevation of OPN and TGF-β1 concentrations and suppressed TNF-α as well as α-SMA levels in hepatic tissue homogenate. Histopathologically, mesalazine as a treatment showed a good restoration of the hepatic parenchymal cells with an obvious decreased intensity and retraction of fibrous proliferation, while as a prophylaxis it didn't achieve enough protection against the harmful effect of TAA, although it decreased the intensity of portal to portal fibrosis and pseudolobulation. Furthermore, mesalazine could suppress the expression of both α-SMA and caspase-3 in immunohistochemical sections. In conclusion, mesalazine could have a potential new indication as anti-fibrotic agent through limiting the oxidative damage and altering TNF-ɑ pathway as an anti-inflammatory drug with down-regulating TGF-β1, OPN, α-SMA and caspase-3 signaling pathways.
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http://dx.doi.org/10.1016/j.cbi.2018.05.002DOI Listing
June 2018

Stimulation of ACE2/ANG(1-7)/Mas Axis by Diminazene Ameliorates Alzheimer's Disease in the D-Galactose-Ovariectomized Rat Model: Role of PI3K/Akt Pathway.

Mol Neurobiol 2018 Oct 7;55(10):8188-8202. Epub 2018 Mar 7.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo, 11562, Egypt.

Overactivation of angiotensin-converting enzyme/angiotensin 2/angiotensin receptor-1 (ACE/Ang2/AT1) axis provokes amyloid-β-induced apoptosis and neurodegeneration in Alzheimer's disease (AD). Moreover, activation of AT1 impairs the survival pathway phosphoinositide 3-kinase/protein kinase B (PI3K/Akt). Interestingly, the coupling between ACE2/Ang(1-7)/Mas receptor (MasR) axis and PI3K/Akt activation opposes AT1-induced apoptosis. However, the effect of in vivo stimulation of MasR against AD and its correlation to PI3K/Akt is not yet elucidated. Thus, the present study aimed to investigate the relationship between PI3K/Akt pathway and the activation of ACE2/MasR in the AD model of D-galactose-ovariectomized rats. AD features were induced following 8-week injection of D-galactose (150 mg/kg, i.p.) in ovariectomized female rats. The ACE2 activator dimenazine (15 mg/kg, i.p.) was daily administered for 2 months. DIZE administration boosted the hippocampal expression of ACE2 and Mas receptors while suppressing AT1 receptor. Notably, dimenazine enhanced the expression of phosphorylated survival factors (PI3K, Akt, signal transducer, and activator of transcription-3) and neuroplasticity proteins such as cyclic adenosine monophosphate-responsive element-binding protein and brain-derived neurotrophic factor along with nicotinic and glutamatergic receptors. Such effects were accompanied by suppressing phosphorylated tau and glycogen synthase kinase3β along with caspase-3, cytochrome-c, nuclear factor kappa B, tumor necrosis factor alpha, and glial fibrillary acidic protein contents. Dimenazine ameliorated the histopathological damage observed in D-galactose-ovariectomized rats and improved their learning and recognition memory in Morris water maze and novel object recognition tests. In conclusion, dimenazine-induced stimulation of ACE2/Ang(1-7)/Mas axis subdues cognitive deficits in AD most probably through activation of PI3K/Akt pathway.
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http://dx.doi.org/10.1007/s12035-018-0966-3DOI Listing
October 2018

Modulating effect of MgO-SiO nanoparticles on immunological and histopathological alterations induced by aflatoxicosis in rats.

Toxicon 2017 Dec 25;140:94-104. Epub 2017 Oct 25.

Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt. Electronic address:

Introduction: AflatoxinB1 (AFB1) is well-known as a feed borne-hepatotoxic and immunosuppressive mycotoxin. This study was conducted to evaluate the efficacy of nanocomposite magnesium oxide and silicon oxide (MgO-SiO) in reducing the toxic effects of AFB1on the immunity and histological alterations in liver, spleen and intestine of adult male rats.

Experimental Design: Animals were divided into a control (Gp1) and three experimental groups (Gps); Gp2 received feed contained 200 ppb AFB1, Gp3 received feed contained 200 ppb AFB1 and 0.5 g/kg MgO-SiO nanocomposite. While, rats of Gp4 received feed contained 0.5 g/kg MgO-SiO nano-composite.

Methods: Cellular and humoral immune responses, as well as histopathological examination and caspase-3 expression in liver, spleen, and intestine, were all evaluated. Residual concentration of AFB1was determined in serum, liver and fecal samples. The obtained data were statistically analyzed.

Results: AFB1markedly reduced body weight gain and food and water consumption. Cellular immune response (total and differential leukocytes count, neutrophils' phagocytic activity, lymphocyte transformation, macrophage activity and serum lysozyme activity), serum total protein, and humoral immune response (fractions of protein as estimated by SDS- PAGE electrophoresis) were all severely reduced by AFB1. Moreover, AFB1induced marked histological alterations and apoptosis in liver, spleen, and intestine.

Conclusion: These findings suggested that the nanocomposite MgO-SiO has high affinity to adsorb AFB1 and can effectively modulate its toxicity in rats.

Impact Statement: Nanocomposite MgO-SiO may offer a novel effective and cheap approach for the preventive management of aflatoxicosis in animals.
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http://dx.doi.org/10.1016/j.toxicon.2017.10.018DOI Listing
December 2017

L-thyroxine modifies nephrotoxicity by regulating the apoptotic pathway: The possible role of CD38/ADP-ribosyl cyclase-mediated calcium mobilization.

PLoS One 2017 11;12(9):e0184157. Epub 2017 Sep 11.

Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

Thyroid hormones are well-established as a key regulator of many cellular metabolic pathways developed in various pathogeneses. Here, we dedicated the current work to investigate the role of thyroid hormone analogue (L-thyroxine, L-TH) in regulating the renal cytotoxicity using in vivo and in vitro models. Swiss mice were exposed to gamma radiation (IRR, 6Gy) or treated with cisplatin (CIS, 15 mg/kg, i.p.) for induction of nephrotoxicity. Remarkably, pretreatment with L-TH (1μg/kg) ameliorated the elevated kidney function biomarkers, oxidative stress and protected the renal tissue from the subsequent cellular damage. Likewise, L-TH inhibited the apoptotic cascade by down-regulating the extreme consumption of the cellular energy (ATP), the expression of caspase-3 and Bax, and the stimulation of cyclic ADP ribose (cADPR)/calcium mobilization. Moreover, incubation with L-TH (120nM/4h) significantly blocked the cytotoxicity of CIS on Vero cells and the depletion of NAD+ content as well as modified the ADP-ribose cyclase (CD38) enzymatic activity. High doses of L-TH (up to30 nM/4h) inversely increased the radiosensitivity of Vero cells towards IRR (up to 6Gy). On the other hand, L-TH did not interfere CIS-induced cytotoxicity of colorectal adenocarcinoma (Caco-2) cell line. In conclusion, pretreatment with L-TH could be a promising protective approach to the renal cellular damage induced during either CIS or IRR therapy by regulating the unbalanced oxidative status, the expression of pro-apoptotic biomarkers via modulation of cADPR mediated-calcium mobilization.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0184157PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593187PMC
October 2017

Epigallocatechin-3-Gallate: The Prospective Targeting of Cancer Stem Cells and Preventing Metastasis of Chemically-Induced Mammary Cancer in Rats.

Am J Med Sci 2017 07 6;354(1):54-63. Epub 2017 Mar 6.

Department of Pathology, Animal Health Research Institute, Dokki, Egypt.

Background: Cancer stem cells are a subpopulation of tumor cells that are capable of self-renewal, capable of tumor recurrence and metastasis, and in addition are resistant to current cancer therapies. Epigallocatechin-3-gallate is a type of catechin found in green tea that is known for its powerful chemoprotective ability. Hence, this study aimed to investigate the effect of epigallocatechin-3-gallate on 7, 12 dimethylbenzanthracene-induced tumor metastasis, angiogenesis and cancer stem cells.

Materials And Methods: For this purpose, 3 groups of virgin femal rats with 7,12 dimethylbenzanthracene-induced mammary cancer were treated using epigallocatechin-3-gallate, paclitaxel or their combination.

Results: It was found that epigallocatechin-3-gallate exhibited significant chemopreventive effects and anti-cancer stem cell activity through several pathways, including a significant decrease in the size and number of tumors per rat, significant amelioration of the oxidative stress markers' alterations and significant inhibition of CD44, VEGF, Ki-67 and MMP-2 expression associated with a significantly increased expression of caspase-3. Histopathologically, therapy with epigallocatechin-3-gallate resulted in marked necrosis of the neoplastic cells and the tumor masses were mostly replaced by proliferated fibrous tissue so that histological confirmation of a previous tumor was not possible at that site. However, in the combination therapy the neoplastic cells showed marked vacuolation, haphazard arrangement and extensive nuclear pyknosis accompanied with many apoptotic bodies. Therapy with the sole paclitaxel caused variable degrees of necrosis among the neoplastic cells. Additionally, the combination of epigallocatechin-3-gallate and paclitaxel significantly enhanced the later anticancer efficacy.

Conclusions: Epigallocatechin-3-gallatecould be offered as an unprecedented curative strategy to eradicate cancer.
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http://dx.doi.org/10.1016/j.amjms.2017.03.001DOI Listing
July 2017

The mitigative effect of Raphanus sativus oil on chromium-induced geno- and hepatotoxicity in male rats.

J Adv Res 2016 May 5;7(3):413-21. Epub 2016 Mar 5.

Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Egypt.

To study the impact of radish oil on the possible genotoxic and hepatotoxic effects of hexavalent chromium, male rats were divided into 4 groups. Group 1 served as control, group 2 received radish oil at the recommended human therapeutic dose (0.07 mL/kg) by gavage, group 3 received sodium dichromate dihydrate (SDD) 520 mg/L in drinking water, and group 4 received both SDD and radish oil as previously mentioned in groups 2 and 3. All treatments were continued for six months. The results revealed that chromium exposure promoted oxidative stress with a consequently marked hepatic histopathological alterations, increased serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, alfa fetoprotein (AFP) levels, and micronucleated erythrocytes (MNE) % in peripheral blood. Moreover, COMET assay of hepatic DNA revealed that SDD exposure significantly decreased the intact cells %, head diameter, and head DNA % compared to control, indicating DNA damage. However, radish oil co-administration with SDD resulted in marked amendment in the altered parameters as detected by improved liver function markers (ALT and ALP) and AFP level, decreased lipid peroxidation, increased antioxidant markers, inhibited hepatic DNA damage and restored the hepatic histology by preventing the appearance of the altered hepatocytes' foci and decreasing chromium induced histopathological lesions. It could be concluded that radish oil was able to provide a convergent complete protection against the geno- and hepatotoxicity of chromium by its potent antioxidant effect.
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http://dx.doi.org/10.1016/j.jare.2016.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4856824PMC
May 2016

The Remedial Efficacy of Spirulina platensis versus Chromium-Induced Nephrotoxicity in Male Sprague-Dawley Rats.

PLoS One 2015 1;10(6):e0126780. Epub 2015 Jun 1.

Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

This study was conducted to investigate the possible protective effect of Spirulina platensis against chromium-induced nephrotoxicity. A total of 36 adult male Sprague-Dawley rats were divided into 4 equal groups (Gps). Gp1 served as control, rats of Gps 2, 3, and 4 were exposed to Spirulina platensis (300 mg/kg b.wt per os) and sodium dichromate dihydrate (SDD) via drinking water at concentration of 520 mg /l respectively. Chromium administration caused alterations in the renal function markers as evidenced by significant increase of blood urea and creatinine levels accompanied with significant increase in kidney's chromium residues and MDA level as well as decreased catalase activity and glutathion content in kidney tissue. Histologically, Cr provoked deleterious changes including: vascular congestion, wide spread tubular epithelium necrobiotic changes, atrophy of glomerular tuft and proliferative hyperplasia. The latter was accompanied with positive PCNA expression in kidney tissues as well as DNA ploidy interpretation of major cellular population of degenerated cells, appearance of tetraploid cells, high proliferation index and high DNA index. Morphometrical measurements revealed marked glomerular and tubular lumen alterations. On contrary, spirulina co-treatment with Cr significantly restored the histopathological changes, antioxidants and renal function markers and all the previously mentioned changes as well.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0126780PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450866PMC
February 2016

Neuropathology of aluminum toxicity in rats (glutamate and GABA impairment).

Pharmacol Res 2003 Mar;47(3):189-94

Faculty of Veterinary Medicine, Department of Pathology, Cairo University, Giza 12211, Egypt.

To get better insights into the pathological and biochemical defects underlying aluminum toxicity in brain tissue, we exposed male albino rats for 35 days to aluminum sulfate by gavage. Tissue aluminum level of brain was assessed, histological sections of brain were examined and amino acid transmitters contents were detected by reversed phase high performance liquid chromatography. Aluminum levels were high in brain specimens of the treated groups comparing to the control and it was dose-dependent. Marked increase in glutamate and glutamine levels was noticed while GABA level was significantly decreased. The most pronounced changes in brain tissue included spongioform changes in the neurons specially those of hippocampus, nuclear deformity, and neurofibrillary degeneration, similar to neurofibrillary tangles in Alzheimer's disease. It is concluded that accumulated aluminum in brain and altered amino acid neurotransmitters are important mechanisms of aluminum neurotoxicity.
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http://dx.doi.org/10.1016/s1043-6618(02)00336-5DOI Listing
March 2003