Faculty Of Pharmacy Research Paper

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1 of 1 Eicosapentaenoic Acid and Vitamin E Against Doxorubicin-Induced Cardiac and Renal Damages: Role of Cytochrome c and iNO
(ACAD MEDICAL SCIENCES I R IRAN, 2018) Fayez, Ahmed M.; Zaafan, Mai A.
Background: 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-alpha) 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-alpha 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.
1,2 Propanediol utilization by Lactobacillus reuteri DSM 20016, role in bioconversion of glycerol to 1,3 propanediol, 3-hydroxypropionaldehyde and 3-hydroxypropionic acid
(ELSEVIER, 06/01/2013) Amin, Heba M; Hashem, Abdelgawad M; Ashour, Mohamed S; Hatti-Kaul, Rajini
The objective of the presented work is to demonstrate the metabolism of 1,2 propandiol by Lactobacillus reuteri and to elucidate the metabolites produced during the process. This Metabolic pathway is crucial for biotechnological applications using L. reuteri in bioconversion of glycerol to industrially important plate-form chemicals. L. reuteri grown on minimal media containing 1,2 propanediol was able to utilize the compound as a sole carbon and energy source. The growth of the bacteria was linear with time; however the specific growth rate was significantly low compared to bacteria grown on the same media in the presence of glucose.
5-Fluorouracil induces plasmonic coupling in gold nanospheres: New generation of chemotherapeutic agents
(2012) Mohamed M.B.; Adbel-Ghani N.T.; El-Borady O.M.; El-Sayed M.A.; National Institute of Laser Enhanced Sciences (NILES); Cairo University; Giza; Egypt; NanoTech Egypt for Photoelectronics; Dreamland; October city; Egypt; Chemistry Department; Cairo University; Giza; Egypt; Chemistry Department; Modern Science and Arts University; October city; Egypt; Laser dynamics laboratory; Georgia Institute of Technology; Atlanta; United States
Loading 5- Fluorouracil (5-FU) into gold nanoparticles (AuNPs) could enhance its activity as anticancer drug hugely by enhancing its ability for penetration through the cell membrane. Accordingly, this work is devoted to loading 5-FU into AuNPs surface and studying the binding mechanism of the drug to the surface of the gold nanoparticles. Our finding indicates that new absorption band appears at longer wavelength upon loading 5-FU into gold nanospheres capped with citrate. This near IR band is due to induced surface plasmon coupling via hydrogen bonding between 5-FU and surface capping AuNPs. This leads to great enhancement of the drug action as chemotherapeutic as well as photothermal agents. Factors which affect the binding between 5-FU and the AuNPs such as pH, time after mixing the drug with AuNPs, concentration of the 5-FU, have been studied in detail. Accordingly, the binding interaction is proven to be via hydrogen bonding. Upon the investigation of thermal and photo satiability, the formed composite 5-FU@AuNPs showed high stability towards these factors. The spectral and morphological studies were measured via UV-VIS spectroscopy and Transmission Electron Microscopy (HR-TEM). Remarkable increases in the drug anticancer activity upon loading into AuNPs were observed for the cell viability test of human colon cancer (HCT16). � 2012 Mohamed MB, et al.
99mTc-amitrole as a novel selective imaging probe for solid tumor: In silico and preclinical pharmacological study
(Elsevier, 2015) Essa, BM; Sakr, TM; A Khedr, Mohammed; El-Essawy, FA; El-Mohty, AA
Lactoperoxidase (LPO) inhibitors are very selective for solid tumor due to their high binding affinity to the LPO enzyme. A computational study was used to select top-ranked LPO inhibitor (alone and in complex with 99mTc) with high in silico affinity. The novel prepared 99mTc-amitrole complex demonstrated both in silico and in vivo high affinity toward solid tumors. 99mTc-amitrole was radio-synthesized with a high radiochemical yield (89.7 ± 3.25). It showed in vitro stability for up to 6 h. Its preclinical evaluation in solid tumor-bearing mice showed high retention and biological accumulation in solid tumor cells with a high Target/Non-Target (T/NT) ratio equal to 4.9 at 60 min post-injection. The data described previously could recommend 99mTc-amitrole as potential targeting scintigraphic probe for solid tumor imaging
99mTc–meropenem as a potential SPECT imaging probe for tumor hypoxia
(SPRINGER, 2012) Sakr, TM; Motaleb, MA; Ibrahim, IT
Meropenem was successfully radiolabeled with 99mTc in high labeling yield (92 ± 2%) and stability (~6 h). 99mTc–meropenem showed high accumulation in tumor hypoxic tissue (4.193% injected dose/g organ). 99mTc–meropenem showed high ability to differentiate the tumor tissue from inflamed or infected tissues in different mice models as its T/NT ratio ~4 in case of tumor mice model while T/NT ratio ~1 in case of inflamed mice model. So, 99mTc–meropenem showed high selectivity in comparison with FDG-PET and 99mTc-nitroimidazole analogues. Thus, 99mTc–meropenem could be used as a selective potential imaging agent for diagnosis of tumor hypoxia.
99mTc-nebivolol as a novel heart imaging radiopharmaceutical for myocardial infarction assessmenta
(SPRINGER, 2013) Sakr, TM; Moustapha, ME; Motaleb, MA
Non-invasive quantification of myocardial β-receptors could become an independent prognostic marker for chronic heart failure and cardiovascular disorders. The aim of this study was to formulate a novel radiopharmaceutical for the detection of myocardial infarction at early stages in susceptible patients, which requires the development of high myocardium affinity radiopharmaceuticals able to establish an accurate in vivo quantification of cardiac β1-adrenoceptors. This was attained by the direct complexation of nebivolol as a cardioselective agent with technetium-99m as one of the most useful radionuclides in diagnostic nuclear medicine. Factors affecting the radiochemical yield such as nebivolol amount, stannous chloride amount, reaction time and pH of the reaction mixture were optimized. The results showed that the radiochemical yield was 95 ± 2.87 % and the radiolabeled compound was separated by high performance liquid chromatography. In vitro studies showed that the formed complex was stable for up to 24 h. In vivo uptake of 99mTc-nebivolol in the heart was 4.55 ± 0.23 % ID/g organ at 0.5 h post injection, whereas the clearance from Albino mice appeared to proceed via the hepatobiliary and renal clearance pathways. Predosing mice with cold nebivolol reduced the heart uptake to 1.1 ± 0.02 % and further confirmed the high specificity and selectivity of this radiotracer for the assessment of the myocardial β1-adrenoceptors
A comparative UPLC‑orbitrap‑MS‑based metabolite profiling of three Pelargonium species cultivated in Egypt
(Springer Nature, 2024-10-01) Rana M. Merghany; Mohamed A. Salem; Shahira M. Ezzat; Sherifa F. A. Moustafa; Salma A. El‑Sawi; Meselhy R. Meselhy
Several Pelargonium species are cultivated mainly to produce essential oils used in perfume industry and for ornamental purposes. Although the chemical composition and biological activities of their essential oils were extensively investigated, there is limited information about the chemical composition of their non-volatile constituents. In this study, we report an Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS)-based metabolomics approach for the annotation and analysis of various metabolites in three species; P. graveolens, P. denticulatum, and P. fragrans utilizing The Global Natural Product Social Molecular Networking (GNPS) and multivariate data analyses for clustering of the metabolites. A total of 154 metabolites belonging to different classes were annotated. The three species are good sources of coumarins, benzoic acid derivatives, organic acids, fatty acids, and phospholipids. However, the highest level of flavonols (mono- and di-O-glycosides) and cinnamic acid derivatives was found in P. graveolens and P. denticulatum, whereas tannins and flavone C-glycosides were abundant in P. fragrans. The metabolic profiles clarified here provide comprehensive information on the non-volatile constituents of the three Pelargonium species and can be employed for their authentication and possible therapeutic applications.
A comprehensive review of natural compounds and their structure–activity relationship in Parkinson’s disease: exploring potential mechanisms
(Springer Nature, 2024-10-11) Rana M. Merghany; Salma A. El‑Sawi; Asmaa F. Aboul Naser; Shahira M. Ezzat; Sherifa F. A. Moustafa; Meselhy R. Meselhy
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine-producing cells in the Substantia nigra region of the brain. Complementary and alternative medicine approaches have been utilized as adjuncts to conventional therapies for managing the symptoms and progression of PD. Natural compounds have gained attention for their potential neuroprotective effects and ability to target various pathways involved in the pathogenesis of PD. This comprehensive review aims to provide an in-depth analysis of the molecular targets and mechanisms of natural compounds in various experimental models of PD. This review will also explore the structure–activity relationship (SAR) of these compounds and assess the clinical studies investigating the impact of these natural compounds on individuals with PD. The insights shared in this review have the potential to pave the way for the development of innovative therapeutic strategies and interventions for PD.
A cutting edge potentiometric determination of baricitinib in synthetic wastewater and in tablet dosage form using modified carbon paste ion-selective membrane
(Elsevier Inc., 2024-09-21) Heba T. Elbalkiny; Mona S. Elshahed; Dalia Mohamed; Azza A. Ashour; Rasha Th. El-Eryan
After the recent hit of COVID-19, many drugs were successively administered to save patients’ lives and those drugs reached aquatic sources, one of those drugs was Baricitinib. Driven by the current situation, a potentiometric technique using an ion-selective membrane (ISM) recipe drop cast on a modified carbon paste electrode was optimized for the superior determination of Baricitinib (BAR). The molecular docking was customized to optimize the proper ionophores incorporated in the ISM, revealing that beta-cyclodextrin (β-CD) is the most compatible ionophore with the studied drug. A multivariate optimization experimental design was employed to optimize the best experimental condition for the analytical method. To this end; dual nanoparticles (multi-walled carbon nanotubes and copper oxide nanoparticles) were incorporated in the carbon paste electrode, and the ISM recipe was enriched with β-CD and cation-exchanger (phosphotungstic acid) in a polyvinylchloride matrix plasticized with dibutyl phthalate. A Nernstian slope equal to 19.97 mV/decade with a linearity range of 7.99 × 10−7–1.00 × 10−3 M was obtained. The validated sensor exhibited good recovery when used to determine the studied drug in synthetic wastewater and tablet dosage form. The greenness of the method was evaluated using the Complementary Green Analytical Procedure Index and Blue Applicability Grade Index.
A sustainable and green HPLC-PDA technique for the simultaneous estimation of Post-COVID-19 syndrome co-administered drugs with greenness and whiteness assessment
(Nature Publishing Group, 2024-10-01) Passant M. Medhat; Manal Mohamed Fouad; Hany H. Monir; Nermine S.Ghoniem
COVID-19 has been a growing global concern in the past four years. Several syndromes associated with this multi-organ viral infection have been observed since the outbreak. According to estimates, 10–15% of people with SARS-CoV- infection may have post-COVID-19 syndrome. Even months after infection, common residual signs and symptoms include myalgia, exhaustion, shortness of breath, rapid heartbeat, stroke, and memory and cognitive impairment which can negatively affect survivors’ quality of life and may consequently lead to their death. Therefore, it is necessary to think about potential therapy options for dealing with both short and long-term impacts. Paracetamol (a common analgesic and antipyretic) and Dexketoprofen Trometamol (a non-steroidal anti-inflammatory drug) are used together to relieve post-COVID symptoms like myalgia (muscle pain) and headache. Additionally, to prevent thrombotic events, Rivaroxaban is recommended for 35 days following discharge. Thus an eco-friendly HPLC-DAD technique was developed for simultaneous quantification of Paracetamol, Dexketoprofen Trometamol, and Rivaroxaban which are co-administered for treatment of post-COVID-19 syndrome. The suggested method was found to be linear in the concentration ranges of 3.00–45.00 µg/mL, 0.5–50.00 µg/mL, and 0.15–20.00 µg/mL, and a limit of detection down to 0.531 µg/mL, 0.095 µg/mL and 0.047 µg/mL for Paracetamol, Dexketoprofen Trometamol and Rivaroxaban, respectively. This method was effectively used to quantify the studied drugs in their bulk powder and spiked human plasma with high percentage recoveries (96.55–99.46%). The suggested approach was validated per International Conference on Harmonization (ICH) requirements and found to be within the acceptable ranges. The method was developed using Green Analytical Chemistry (GAC) principles, with the solvents used and run time having a significant effect on the method’s greenness. “Non-toxic” ethanol served as the organic modifier in the mobile phase, moreover, the total run time was 12 min making it suitable for the routine analysis of the mentioned drugs in plasma samples. To get a full image of the method’s greenness profile; two most recent greenness assessment tools, the Green Analytical Procedure Index (GAPI), and the Analytical GREEnness metric (AGREE), were employed, with White Analytical Chemistry (WAC) principles proving its environmental safety.
Accurate Prediction of Advanced Liver Fibrosis Using the Decision Tree Learning Algorithm in Chronic Hepatitis C Egyptian Patients
(HINDAWI LTD, 2016) Hashem, Somaya; Esmat, Gamal; Elakel, Wafaa; Habashy, Shahira; Raouf, Safaa Abdel; Darweesh, Samar; Soliman, Mohamad; Elhefnawi, Mohamed; El-Adawy, Mohamed; ElHefnawi, Mahmoud
Background/Aim. Respectively with the prevalence of chronic hepatitis C in the world, using noninvasive methods as an alternative method in staging chronic liver diseases for avoiding the drawbacks of biopsy is significantly increasing. The aim of this study is to combine the serum biomarkers and clinical information to develop a classification model that can predict advanced liver fibrosis. Methods. 39,567 patients with chronic hepatitis C were included and randomly divided into two separate sets. Liver fibrosis was assessed via METAVIR score; patients were categorized as mild to moderate (F0-F2) or advanced (F3-F4) fibrosis stages. Two models were developed using alternating decision tree algorithm. Model 1 uses six parameters, while model 2 uses four, which are similar to FIB-4 features except alpha-fetoprotein instead of alanine aminotransferase. Sensitivity and receiver operating characteristic curve were performed to evaluate the performance of the proposed models. Results. The best model achieved 86.2% negative predictive value and 0.78 ROC with 84.8% accuracy which is better than FIB-4. Conclusions. The risk of advanced liver fibrosis, due to chronic hepatitis C, could be predicted with high accuracy using decision tree learning algorithm that could be used to reduce the need to assess the liver biopsy.
Acovenoside A as a novel therapeutic approach to boost taxol and carboplatin apoptotic and antiproliferative activities in NSCLC: Interplay of miR-630/miR- 181a and apoptosis genes
(Academic Press Inc., 2023-07) Aborehab, Nora M; Abd-Elmawla, Mai A; ElSayed, Abeer M; Sabry, Omar; Ezzat, Shahira M; Abd-Elmawla, Mai A; ElSayed, Abeer M; Sabry, Omar
The aim of the present study is to explore the potential anticancer effect of the cardenolide; 2 acovenoside A against non-small cell lung cancer, understand its molecular mechanism in inducing 3 apoptosis and show the effect of its combination with carboplatin and taxol. MTT assay showed that the 4 combination of acovenoside A with taxol and carboplatin caused 78.9% cytotoxicity reflecting the 5 synergistic effect. The triple combination showed the best growth inhibition efficiency where the 6 number of cells at the G2/M phase was decreased and boosted up apoptotic and necrotic activity. The 7 combination also showed the most remarkable increase in gene expression of Bax and p53 and the least 8 level of Bcl2. The gene expression of miRNA181a and miRNA630 was significantly upregulated in cell 9 lines treated with the combination. The present study has proven that the underlying mechanism of 10 acovenoside A is partially attributed to the upregulation of miR-630 and miR-181a gene expressions 11 which in turn targets the intrinsic apoptosis genes as p53, Bax and Bcl2 as well as caspase 3. The present 12 study is the first to address the valuable effect of using acovenoside A together with carboplatin and 13 taxol in the treatment of NSCLC via exerting apoptotic, antiproliferative, and cytotoxic ef
Acovenoside A Induces Mitotic Catastrophe Followed by Apoptosis in Non-Small-Cell Lung Cancer Cells
(American Chemical Society, 2017) El Gaafary M.; Ezzat, Shahira M; El Sayed A.M.; Sabry O.M.; Hafner S.; Lang S.; Schmiech M.; Syrovets T.; Simmet T.; Department of Pharmacognosy; College of Pharmacy; Cairo University; Giza; 11562; Egypt; Pharmacognosy Department; Faculty of Pharmacy; October University for Modern Sciences and Arts (MSA); Cairo; 11562; Egypt; Institute of Pharmacology of Natural Products and Clinical Pharmacology; Ulm University; Ulm; D-89081; Germany
We investigated the cytotoxic potential of the cardenolide glycoside acovenoside A against non-small-cell lung cancer cells. Lung cancer is the leading cause of cancer-related mortality and the second most common cancer diagnosed. Epidemiological studies revealed a direct correlation between the regular administration of cardiac glycosides and a lower incidence of various cancers. Acovenoside A, isolated from the pericarps of Acokanthera oppositifolia, potently inhibited proliferation and induced cytotoxicity in A549 non-small-cell lung cancer cells with an IC 50 of 68 � 3 nM after 48 h of exposure. Compared to the antineoplastic agent doxorubicin, acovenoside A was more potent in inhibiting the viability of A549 cancer cells. Moreover, acovenoside A exhibited selectivity against cancer cells, being significantly less toxic to lung fibroblasts and nontoxic for peripheral blood mononuclear cells. Analysis of the cell cycle profile in acovenoside A-treated A549 cells revealed mitotic arrest, due to accumulation of the G 2 /M regulators cyclin B 1 and CDK1, and cytokinesis failure. Furthermore, acovenoside A affected the mitochondrial membrane integrity and induced production of radical oxygen species, which resulted in induction of canonical apoptosis, manifested by caspase 3 activation and DNA fragmentation. Based on our results, acovenoside A warrants further exploration as a potential anticancer lead. � 2017 The American Chemical Society and American Society of Pharmacognosy.
Acylated flavonol diglucosides from Ammania auriculata
(Verlag der Zeitschrift fur Naturforschung, 2015) Nawwar M.; Ayoub N.; El-Raey M.; Zaghloul S.; Hashem A.; Mostafa E.; Eldahshan O.; Lindequist U.; Linscheid M.W.; National Research Center; Department of Phytochemistry and Plant Systematics; El Bohooth Str.; P.O. 12622; Dokki; Cairo; Egypt; Faculty of Pharmacy; Department of Pharmacognosy; Ain-Shams University; Cairo; Egypt; October University for Modern Sciences and Arts; 6th October City; Egypt; Department of Pharmacognosy; Faculty of Pharmacy; Institute of Pharmacy; Pharmaceutical Biology; Ernst-Moritz-Arndt-Universit�t Greifswald; Greifswald; Germany; Laboratory of Applied Analytical and Environmental Chemistry; Department of Chemistry; Humboldt-Universit�t zu Berlin; Berlin; Germany
Chemical investigation of the extract of the whole Ammania auriculata plant resulted in the identification of 13 polyphenols, including the hitherto unknown flavonoids, kaempferol 3-O-?-(6?-galloylglucopyranoside)- 7-O-?-glucopyranoside, and its quercetin analogue. The structures of all isolates were elucidated by conventional methods, spectroscopic analysis, including 1D and 2D NMR, and by HRESI-MS as well.
Adaptation of Hard Gelatin Capsules for Aqueous Solution Delivery Using Gamma Radiation
(JAPR, 2017-10) Sakr, Tamer; Assaly, Mohamed K.; AbdelRashid, Rania S; Omar, Samia
Objective: Directly incorporating aqueous solutions into hard gelatin capsules (HGCs) without dispersing them in an oily medium is considered a challenge for most researchers and manufacturers. The aim of the study is to evaluate the effect of gamma radiation (ɣ-radiation) on the adaptation of HGCs for aqueous solution delivery. Methods: Empty HGC shells were exposed to four of ɣ-radiation doses (1, 3, 5, 10 kGy). Then, the physicochemical properties of irradiated capsules were evaluation and compared with those of non-irradiated capsules. Fourier-transform infrared spectroscopy (FT-IR), capsule hardness, and water incorporation tests were performed. In-vitro disintegration/dissolution behavior determined as (rupture time) in different dissolution media was evaluated. Results: The results showed direct proportionality between the ɣ-radiation dose and HGC crosslinking degree up to 3 kGy, while at doses >3 kGy, degradation rather than crosslinking occurred. The results were clearly demonstrated by FTIR as peptide linkages between gelatin molecules. All the ɣ-irradiated HGCs submitted to hardness test were completely deformed without rupture with increasing capsule deformation work (J) for γ-radiation doses up to 3 kGy; the deformation work declined at doses >3 kGy. The water incorporation study revealed that capsules exposed to 3 kGy could hold up to 100 ml of methylene blue solution without deformation or leakage for 45 minutes compared with non-irradiated HGCs, which showed a significantly lower tolerance of only 2 minutes (p<0.001). The crosslinking of HGCs had a minor significant effect on in-vitro rupture time, especially at gastric pH. Conclusion: The irradiation technique may be used not only for sterilizing HGCs but also for adapting HGCs for aqueous solutions delivery, as it showed a significant positive effect, which was optimal at a dose of 3 kGy. However, these results are not sufficient for scaled-up manufacturing; thus, further investigations are strongly recommended.
Adaptation of hard gelatin capsules for oral delivery of aqueous radiopharmaceuticals
(Springer, 2019) Omar S.M.; Abdel-Rashid R.S.; AlAssaly M.K.; Sakr T.M.; Faculty of Pharmacy; Ahram Canadian University; Giza; Egypt; Department of Pharmaceutics and Industrial Pharmacy Faculty of Pharmacy; Helwan University; Ain Helwan; Cairo; 11795; Egypt; Ministry of Interior; Medical Services; Cairo; Egypt; Faculty of Pharmacy; October University of Modern Sciences and Arts; Cairo; Egypt; Radioactive Isotopes and Generators; Atomic Energy Authority; Cairo; Egypt
Purpose: Oral administration of Iodine?131 (I?131) solutions causes high risk of contamination for patients and dispensers. The objective of the study was to adapt hard gelatin capsules (HGCs) for filling with radiopharmaceutical solutions without deformation. Methods: Polystyrene (PS) internally lining films with different thicknesses were used to protect HGCs. The insulated HGCs were evaluated for their physicochemical characteristics and rupturing time in different dissolution media. HGCs internally lined with PS were examined for withstand loading with different volumes and radioactivities of I?131 solutions. Radioactivity release was studied in deionized water and acidic media. Quality control of released I?131 was inspected for radiochemical purities. Results: There was a directly proportion between PS lining thickness and stability of HGCs after filling with 500�?l aqueous methylene blue solution. HGCs internally lined with PS 100�?m thickness withstand deformation for ? two months; however showed fast in-vitro rupturing time in different dissolution media. Internally lined HGCs loaded with different volumes and radioactivities of I?131 solutions resisted for one week without radioactive leakage. Yet, revealed complete release of I?131 after 20�min in dissolution media with great radiochemical purity. Conclusion: The study promises safely I?131 aqueous solution delivery via adapted HGCs. [Figure not available: see fulltext.]. � 2019, Springer Nature Switzerland AG.
Addressing the link between paraoxonase-1 gene variants and the incidence of early onset myocardial infarction
(2015) F. Abdel Rahman, Mohamed; M. Hashad, Ingy; Abou-Aisha, Khaled; M. Abdel-Maksoud, Sahar; Z. Gad, Mohamed
The enzyme paraoxonase-1 (PON1) represents an endogenous defense mechanism against vascular oxidative stress, thereby contributing to the prevention of atherosclerosis. Several polymorphisms have been reported in the PON1 gene, including Q192R. PON1 phenotype is commonly expressed as the paraoxonase/arylesterase ratio (PON/ARE). The major aim of this study was
Adiponectin (+276 G/T), Tumor Necrosis Factor-alpha (-308 G/A) and Interleukin-6 (-174 C/G) Genes Polymorphisms in Egyptian Type 2 Diabetic Patients
(OMICS INT PVT LTD, 2016-05) Hamid, Amr M. Abdel; Saleh, Samy M; Mesbah, Noha M; Abo-El Matty, Dina M; Abd-Elbaky, Atif E
Type 2 diabetes mellitus (T2DM) is a metabolic pro-inflammatory disorder characterized by chronic hyperglycemia and increased levels of circulating cytokines. Adiponectin, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (Il-6), are important cytokines mediators in the pathogenesis of T2DM. The single nucleotide polymorphisms (SNPs) present in the regulatory regions of cytokine genes often have an impact on their expression levels. Aim: Explore potential associations between SNP+276 G/T of adiponectin, SNP -308 G/A of TNF-alpha and SNP -174 C/G of IL-6 genes with T2DM and to assess its influence on their serum levels. Subjects and Methods: From the Egyptian population, we enrolled 95 T2DM patients and 85 non-diabetic controls. Serum adiponectin, TNF-alpha and IL-6 were measured. Genotyping for three SNPs of the adiponectin, TNF-alpha and IL-6 genes was performed by polymerase chain reaction-restriction fragment length polymorphism. Results: Subjects with the GT/TT genotype of SNP 276 were at increased risk for T2DM (OR=15.88, CI=7.56-33.31, P = 0.01) and associated with hypoadiponectinemia compared with the GG genotype. Furthermore, the allelic frequency of the A allele of SNP 308 was significantly different between T2DM patients compared to controls (X2(=)30.54, P = 0.0001). Moreover, Individuals with T2DM carrying the GA/AA genotypes had significantly higher serum TNF-alpha levels than those carrying GG genotype. In addition, Carriers of G allele of IL-6 were significantly more likely associated with T2DM. Conclusion: Genetics variations in Adiponectin +276 G/T, TNF-alpha 308 G/A and IL-6 -174 C/G may contribute to the disposition for T2DM in Egyptian patients.
Adiponectin and E-selectin concentrations in relation to inflammation in obese type 2 diabetic patients with coronary heart disease(s)
(2011) El-Mesallamy H.O.; Hamdy N.M.; Salman T.M.; Mahmoud S.; Biochemistry Department; Faculty of Pharmacy; Ain Shams University; Cairo; Egypt; Biochemistry Department; Faculty of Pharmacy; AL-Azhar University; Cairo; Egypt; Modern Sciences and Arts University; Cairo; Egypt
Aim. Adipose tissue is now regarded as a source of proinflammatory mediators which may contribute to vascular injury, insulin resistance (IR), and atherogenesis, however, some of them have a protective role against vascular inflammation and/or IR; namely adiponectin and nitric oxide (NO). Adiponectin is a fat derived hormone, which enhances insulin sensitivity. In experimental studies adiponectin was shown to have anti-atherogenic properties by suppressing endothelial expression of adhesion molecules as endothelial-selectin (E-selectin) and inflammatory cytokines as high-sensitivity C-reactive protein (hsCRP), interleukin-1? (IL-1?), and monocyte chemotactic protein-1 (MCP-1). Therefore, the aim of the study was to evaluate plasma adiponectin, E-selectin, hsCRP, IL-1?, and MCP-1 concentrations in obese patients with and without coronary heart disease (CHD) having type 2 diabetes mellitus (DM) and evaluation of their relationship with selected anthropometric, biochemical, and clinical parameters. Methods. The study group consisted of (N.=70) males, 20 of which served as healthy non-obese controls (group I) (mean age 38.53.7 years; mean BMI 28 1.2 kg/m2). Patients enrolled in the study were classified into the following groups: type 2 DM obese subjects without CHD (group II) (N.=25) (mean age 42.23 years; mean BMI 32.11.4 kg/m2) and type 2 DM obese subjects with CHD (group III) (N.=25) (mean age 40.63 years; mean BMI 31.51.2 kg/m 2). Glucose and insulin estimation was performed and insulin resistance index (HOMA-IR) was calculated. In the fasting state, the plasma HbA1c, adiponectin, E-selectin, in comparison to hsCRP, IL-1?, MCP-1, and lipid parameters were estimated. Results. FBG, HbA 1c%, lipids, insulin, MDA, NO, hsCRP, IL-?, MCP-1, Adiponectin as well as E-selectin concentration were significantly different in patients with type 2 DM and CHD in comparison to patients without CHD and moreover, the healthy control group (P=0.01). There was a significant negative correlation between adiponectin and E-selectin (r=-0.642; P=0.0001). Conclusion. Our study supports the hypothesis that decreased level of adipokine(s), together with increased oxidative stress, pro-inflammatory marker(s) as well as endothelial adhesion molecule(s) contributes to the complex process of atherosclerosis in type 2 diabetic obese patients that may lead eventually to CHD.
Adiponectin and pro-inflammatory cytokines in obese diabetic boys
(2011) El-Mesallamy H.O.; Hamdy N.M.; Ibrahim S.M.; Biochemistry Department; Faculty of Pharmacy; Ain Shams University; Cairo; Egypt; Modern Sciences and Arts University; Cairo; Egypt
Adiponectin serum levels were significantly lower in obese diabetic than in non-obese healthy boys (P<0.001). Circulating soluble E-selectin levels was significantly higher in obese diabetic boys than the healthy non-obese (P<0.01). There were significant inverse correlations between adiponectin and sE-selectin, hsCRP, IL-1?, and MCP-1 and positively with NOx. We conclude that sE-selectin and MCP-1 may represent a link between obesity and related co-morbidities in children and adults.

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