Browsing by Author "Fayez A.M."
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Item Alpha lipoic acid exerts antioxidant effect via Nrf2/HO-1 pathway activation and suppresses hepatic stellate cells activation induced by methotrexate in rats(Elsevier Masson SAS, 2018) Fayez A.M.; Zakaria S.; Moustafa D.; Department of Pharmacology and Toxicology; Faculty of Pharmacy; MSA University; October City 6; Giza; Egypt; Department of Pharmacology and Toxicology; Faculty of Pharmacy; October 6 University; October City 6; Giza; EgyptHepatic injury is a major side effect associated with methotrexate (MTX) therapy resulting from inflammatory reactions and oxidative stress induction. Therefore, liver fibrosis incidence is augmented with long-term MTX therapy. Alpha lipoic acid (ALA) is a naturally occurring compound with potent antioxidant activity. This study explored the hepatoprotective mechanisms of ALA against MTX-induced hepatic injury in rats. Hepatic injury was induced in MTX group by 20 mg/kg body weight ip. injection of MTX. ALA group was pretreated with ALA 60 mmol/kg body weight ip. for five days followed by a single dose of MTX in the sixth day. Blood samples and liver tissues were then obtained to assess several biochemical parameters as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), reduced glutathione (GSH), total antioxidant capacity (TAC) and lipid peroxidation. Nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway was studied by determining the extent of mRNA Nrf2 expression and the level of HO-1. Hepatic stellate cells (HSCs) activation was evaluated by estimating the expression of ?-smooth muscle actin (?-SMA) and hydroxyproline content. Also, tumor necrosis factor alpha (TNF-?), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and caspase-3 were assessed by ELISA in addition to histopathological examination of liver samples. Results showed that ALA pretreatment improved liver function since serum ALT, AST and ALP levels were reduced. Additionally, ALA restored GSH and TAC levels when compared to MTX group and decreased lipid peroxidation. ALA exerted its antioxidant effect via Nrf2/HO-1 pathway as well as it showed anti-inflammatory and antiapoptotic effects by reducing TNF-? iNOS, COX-2 and caspase-3 levels in liver tissue homogenate. Finally, ALA suppressed HSCs activation by decreasing ?-SMA expression and hydroxyproline content in liver. It was concluded that ALA has hepatoprotective effects against MTX-induced hepatic injury mediated by Nrf2/HO-1 pathway as well as anti-inflammatory and antiapoptotic properties. � 2018 Elsevier Masson SASItem Carbamazepine loaded vesicular structures for enhanced brain targeting via intranasal route: Optimization, in vitro evaluation, and in vivo study(Innovare Academics Sciences Pvt. Ltd, 2019) Yassin G.E.; Amer R.I.; Fayez A.M.; Department of Pharmaceutics and Industrial Pharmacy; Faculty of Pharmacy; Al Azhar University; Cairo; Egypt; Department of Pharmaceutics; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); Giza; Egypt; Department of Pharmacology; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); Giza; EgyptObjective: Carbamazepine (CBZ) is used as a first line in the treatment of grand mal and partial seizures, but it suffers from many side effects on different systems of the body. The objective of the present study was optimization of CBZ vesicular structures using 23 multifactorial design for the most efficient targeting of CBZ to the brain via the intranasal route. Methods: The concentration of CBZ (10 and 20%), type of vesicles (niosomes and spanlastics) and speed of rotation (200 and 300 rpm) were considered as the independent variables XA, XB and XC respectively, while the dependent variables were particle size PS (Y1), polydispersity index PDI (Y2), zeta potential ZP (Y3) and entrapment efficiency EE (Y4). The study of the effect of different formulation variables was carried out using Design-Expert �� software. CBZ-loaded spanlastics and noisome were prepared by the ethanol injection method and thin film hydration method, respectively. The optimized formulation was subjected to viscosity measurement, in vitro drug release and physical stability studies. In vivo evaluations in rats for the optimized formulation in comparison to oral CBZ suspension was carried out using behavioral assessment by elevated plus maze test, determination of endothelial nitric oxide synthase (e-NOS), reduced glutathione (GSH) and ELISA estimation of TNF��. Results: The selected optimized formulation (F0) containing 20% CBZ and spanlastic vesicular structure showed PS, PDI, ZP, and the EE % of 350.09 nm, 0.830, 16.124mV and 82.777%, respectively. In vitro release study of F0 demonstrated the ability of the F0 to increase drug release in the range time from 10-60 min (p<0.05) when compared with CBZ suspension. The viscosity of F0 was nearly uniform (65 cps). The photomicrograph taken by the transmission electron microscopy (TEM) reveals the spherical shape of F0. Good physical stability for six months of storage at 25�a C was found for F0. The optimized spanlastic formulation F0 showed a decrease in latency time in behavior assessment test using elevated plus Maze test, a decrease in serum eNOS and TNF-�� and increase in GSH when compared with the oral CBZ suspension, in addition to the histopathological study that revealed the more CBZ uptake by the brain. Conclusion: The optimized spanlastic formulation F0 achieved better results when compared with the oral CBZ suspension for targeting the CBZ spanlastics vesicular structure to the brain via the nasal route. � 2019 The Authors.Item Comparative lyophilized platelet-rich plasma wafer and powder for wound-healing enhancement: formulation, in vitro and in vivo studies(Taylor and Francis Ltd., 2019) Yassin G.E.; Dawoud M.H.S.; Wasfi R.; Maher A.; Fayez A.M.; Department of Pharmaceutics and Industrial Pharmacy; Faculty of Pharmacy; Al Azhar University; Cairo; Egypt; Department of Pharmaceutics; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA University); Giza; Egypt; Department of Microbiology; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA University); Giza; Egypt; Department of Biochemistry; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA University); Giza; Egypt; Department of Pharmacology; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA University); Giza; EgyptPlatelet-rich plasma (PRP) accelerates wound healing, as it is an excellent source of growth factors. PRP was separated from whole human blood by centrifugation. PRP powder and wafers were prepared by lyophilization, with the wafers prepared using sodium carboxymethylcellulose (Na CMC). The PRP wafers showed porous structures, as indicated by scanning electron microscopy (SEM) images, and the ability of the wafer to absorb exudates and thus promote wound healing was tested with the hydration capacity test. The platelet count was tested and indicated that the presence of PRP in the wafers had no effect on the platelet count. An antimicrobial activity test was carried out, showing that PRP had antibacterial activity against Gram-negative bacteria. Compared with lyophilized PRP powder and PRP-free wafers, PRP wafers showed the highest percent of wound size reduction on induced wounds in rats. Histopathological examination of rat skin showed that the PRP wafers achieved the shortest healing time, followed by the lyophilized PRP powder and finally the PRP-free wafers. The present study revealed that PRP can be formulated as a wafer, which is a promising pharmaceutical delivery system that can be used for enhanced wound-healing activity and improved the ease of application compared to lyophilized PRP powder. 2019, 2019 Informa UK Limited, trading as Taylor & Francis Group.Item Eicosapentaenoic acid and vitamin e against doxorubicin-induced cardiac and renal damages: Role of cytochrome c and inos(Academy of Medical Sciences of I.R. Iran, 2018) Fayez A.M.; Zaafan M.A.; Pharmacology and Toxicology Department; Faculty of Pharmacy; October University for Modern Sciences; Arts; EgyptBackground: The current study aimed to evaluate the mechanisms involved in protection against doxorubicin-induced cardiac and renal toxicities upon treatment with eicosapentaenoic acid and vitamin E. Methods: Rats were randomly assigned to 4 groups: normal control, doxorubicin inducted control, eicosapentaenoic acid treated group and a final group pretreated with vitamin E. Lipid peroxidation, reduced glutathione (GSH) and tumor necrosis factor-alpha (TNF-?) contents as well as glutathione peroxidase (GPx), superoxide dismutase (SOD) and myeloperoxidase (MPO) activities were assessed. Moreover, hearts were used for immunohistochemical detection of the pro-apoptotic protein cytochrome c expression, while the kidneys were used for detection of inducible nitric oxide synthase (iNOS) expression. Results: Eicosapentaenoic acid and vitamin E produced significant protection from doxorubicin-induced cardiac and renal toxicities. The suggested mechanisms for protection included decreased cytochrome c and iNOS expression as well as markedly decreased lipid peroxides and TNF-? contents accompanied with increased GSH content as compared to the doxorubicin control group. Moreover, there was marked increase in GPx and SOD activities accompanied by significant suppression of MPO activity. Conclusion: The present study demonstrated the potent protective effects of eicosapentaenoic acid and vitamin E from doxorubicin induced cardiac and renal toxicities through their potent anti-oxidant, anti-inflammatory and anti-apoptotic properties. Hence, eicosapentaenoic acid and vitamin E could be promising protective agents against doxorubicintoxicity. � 2019, Academy of Medical Sciences of I.R. Iran. All rights reserved.Item Hepatoprotective activity of Erythrina neillii leaf extract and characterization of its phytoconstituents(Elsevier GmbH, 2019) Bakr R.O.; Fayed M.A.A.; Fayez A.M.; Gabr S.K.; El-Fishawy A.M.; Taha S.El-Alfy; Department of Pharmacognosy; Faculty of Pharmacy; October University for Modern Sciences and Arts; Giza; 11787; Egypt; Department of Pharmacognosy; Faculty of Pharmacy; El-Sadat City University; Egypt; Department of Pharmacology; Faculty of Pharmacy; October University for Modern Sciences and Arts; Giza; 11787; Egypt; Department of Pharmacognosy; Faculty of Pharmacy; Cairo University; Cairo; 11562; EgyptBackground: Natural antioxidants and anti-inflammatory agents have the ability to restore normal balance to destructed liver cells. The genus Erythrina has attracted attention for its broad spectrum of physiological activities and its rich polyphenolic and alkaloid contents. Hypothesis/Purpose: The major phytoconstituents of Erythrina neillii, an ornamental coral tree and a hybrid between E. herbacea and E. humeana that was not previously studied, were investigated. The hepatoprotective effect and underlying mechanisms were also assessed. Study design and methods: The main phytoconstituents in the different fractions of the alcoholic leaf extract (dichloromethane and ethyl acetate) were identified using high resolution high-performance liquid chromatography coupled with mass spectrometry (HR-HPLC-MS-MS) based on the fragmentation pattern and molecular formula of the identified compounds and on previous literature. In addition, the hepatoprotective, anti-inflammatory and antioxidant activities of three doses of E. neillii alcoholic leaf extract (100, 250, 500 mg/kg) were investigated in methotrexate (MTX)-intoxicated rats and were compared with those of silymarin-treated rats. Liver function parameters were obtained, and a histopathological study was performed. In addition, the anti-inflammatory mediators and the antioxidant system in the liver tissues were assessed. Results: The dichloromethane extract revealed an abundance of alkaloids (25), in addition to tentatively identifying flavone (1), flavanone (1) and three fatty acids. Additionally, thirty-six compounds belonging to different classes of phytoconstituents with a predominance of flavonoids (21), O/C-flavone and flavonol glycosides, followed by alkaloids (9), fatty acids (4) and (2), and phenolic glycoside were identified in the ethyl acetate extract. Compared with MTX, alcoholic leaf extract (500 mg/kg) ameliorated the MTX-induced alterations by improving several biochemical marker levels, fighting oxidative stress in serum and liver tissues, and decreasing inflammatory mediators; this finding was further confirmed by the histopathological study. Conclusion: This study reveals E. neillii, a rich source of flavonoids and alkaloids, which could be further exploited to provide a promising and safe antihepatotoxic agent source. 2018 Elsevier GmbH