Ernest Adeghate

Emirates University, Arab, Alabama, United States

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Publications (184)395.84 Total impact

  • 05/2015; 2(1). DOI:10.15744/2394-6504.2.101
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    ABSTRACT: Nociceptin has been reported to play an important role in the regulation of pancreatic exocrine secretion. Most of the studies performed on nociceptin are mainly physiological rather than morphological in nature. The present study investigated the pattern of distribution of nociceptin in the endocrine pancreas of normal and diabetic rats. Immunohistochemistry, immunofluorescence, Western blot, and double-labeled immunoelectron microscopy were used in this study. Diabetes was induced using streptozotocin (60 mg/kg body weight). Nociceptin-immunoreactive cells were observed in the central and peripheral regions of the islets of both normal and diabetic rat pancreas. The number of nociceptin-positive cells was significantly (P < 0.05) lower in the islet of diabetic rats compared with the control. Immunofluorescence study showed that nociceptin colocalizes with insulin in pancreatic β-cells. The degree of colocalization of nociceptin with insulin was severely deranged after the onset of diabetes. Moreover, immunogold particles conjugated with either nociceptin or insulin were observed on the granules of pancreatic β-cell. The number of nociceptin-labeled colloidal gold particles was significantly lower after the onset of diabetes. Nociceptin is present in pancreatic islets cells and colocalizes with insulin. Nociceptin may have a physiological role in the metabolism of insulin.
    Pancreas 05/2015; 44(4):602-7. DOI:10.1097/MPA.0000000000000306 · 3.01 Impact Factor
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    ABSTRACT: Water pipe smoking (WPS) is increasing in popularity and prevalence worldwide. Convincing data suggest that the toxicants in WPS are similar to that of cigarette smoke. However, the underlying pathophysiologic mechanisms related to the early pulmonary events of WPS exposure are not understood. Here, we evaluated the early pulmonary events of nose-only exposure to mainstream WPS generated by commercially available honey flavored "moasel" tobacco. BALB/c mice were exposed to WPS 30 min/day for 5 days. Control mice were exposed using the same protocol to atmospheric air only. We measured airway resistance using forced oscillation technique, and pulmonary inflammation was evaluated histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid and lung tissue. Lung oxidative stress was evaluated biochemically by measuring the level of reactive oxygen species (ROS), lipid peroxidation (LPO), reduced glutathione (GSH), catalase, and superoxide dismutase (SOD). Mice exposed to WPS showed a significant increase in the number of neutrophils (P < 0.05) and lymphocytes (P < 0.001). Moreover, total protein (P < 0.05), lactate dehydrogenase (P < 0.005), and endothelin (P < 0.05) levels were augmented in bronchoalveolar lavage fluid. Tumor necrosis factor α (P < 0.005) and interleukin 6 (P < 0.05) concentrations were significantly increased in lung following the exposure to WPS. Both ROS (P < 0.05) and LPO (P < 0.005) in lung tissue were significantly increased, whereas the level and activity of antioxidants including GSH (P < 0.0001), catalase (P < 0.005), and SOD (P < 0.0001) were significantly decreased after WPS exposure, indicating the occurrence of oxidative stress. In contrast, airway resistance was not increased in WPS exposure. We conclude that subacute, nose-only exposure to WPS causes lung inflammation and oxidative stress without affecting pulmonary function suggesting that inflammation and oxidative stress are early markers of WPS exposure that precede airway dysfunction. Our data provide information on the initial steps involved in the respiratory effects of WPS, which constitute the underlying causal chain of reactions leading to the long-term effects of WPS. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
    03/2015; 3(3). DOI:10.14814/phy2.12258
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    ABSTRACT: This paper reviews the blood–brain barrier (BBB) penetration of newly developed pyridinium aldoximes. Pyridinium aldoximes are highly charged hydrophilic compounds used in the treatment of subjects exposed to organophosphonates because they are effective as acetylcholinesterase reactivators. Pyridinium aldoximes have antidotal effects against poisoning with cholinesterase inhibitors, a frequent problem affecting people working with organophosphate-based insecticides and pesticides. Toxic organophosphonate products such as sarin and tabun can be used by terrorists as chemical warfare agents. This poses a severe challenge to all innocent and peace-loving people worldwide. This review gives a brief summary of BBB transporters and description of the current in vitro and in vivo methods for the characterization of BBB penetration of established and novel pyridinium aldoximes. The authors provide a putative mechanism of penetration, outline some future ways of formulation and discuss the possible advantages and disadvantages of increasing BBB penetration. Copyright © 2014 John Wiley & Sons, Ltd.
    Journal of Applied Toxicology 02/2015; 35(2). DOI:10.1002/jat.3048 · 3.17 Impact Factor
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    ABSTRACT: Abstract Context: Hyperlipidemia is known to be a major risk factor for the development of cardiovascular diseases (CVDs) which include atherosclerosis, coronary heart disease, and stroke. Although there are a large number of anti-hyperlipidemic drugs available, unfortunately, they all have side effects. Objective: Terminalia chebula Retz. (Combretaceae) is a plant used to treat cardiac disorders in the traditional Ayurveda medicine in India. The objective of this study was to assess the anti-hyperlipidemic properties of a methanol (MeOH) bark extract of T. chebula. Materials and methods: Acute toxicity studies were performed according to the Organisation for Economic Cooperation and Development (OECD) guideline no. 423 using various doses (5, 50, 300, and 2000 mg/kg) of T. chebula bark. Anti-hyperlipidemic effect of MeOH bark extract of T. chebula at doses of 200, 400, and 600 mg/kg and fasting glucose levels after treatment with MeOH bark extract of T. chebula at doses of 200, 400, and 600 mg/kg were analyzed using commercially available kits. Results: Acute toxicity studies did not show any morbidity and mortality at various doses. The MeOH extract of T. chebula bark at doses of 200, 400, and 600 mg/kg significantly lowered serum cholesterol and triglyceride levels. Moreover, the extract of T. chebula and the positive control atorvastatin-treated groups of animals showed a significant increase in the serum high-density lipoprotein (HDL) cholesterol levels in diet-induced hypercholesterolemic animals. Conclusion: The overall results confirm that the bark extract of T. chebula possesses significant anti-hyperlipidemic activity.
    Pharmaceutical Biology 01/2015; 53(8):1-8. DOI:10.3109/13880209.2014.962058 · 1.34 Impact Factor
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    ABSTRACT: Glucagon is an important pancreatic hormone, released into blood circulation by alpha cells of the islet of Langerhans. Glucagon induces gluconeogenesis and glycogenolysis in hepatocytes, leading to an increase in hepatic glucose production and subsequently hyperglycemia in susceptible individuals. Hyperglucagonemia is a constant feature in patients with T2DM. A number of bioactive agents that can block glucagon receptor have been identified. These glucagon receptor antagonists can reduce the hyperglycemia associated with exogenous glucagon administration in normal as well as diabetic subjects. Glucagon receptor antagonists include isoserine and beta-alanine derivatives, bicyclic 19-residue peptide BI-32169, Des-His1-[Glu9] glucagon amide and related compounds, 5-hydroxyalkyl-4-phenylpyridines, N-[3-cano-6- (1,1 dimethylpropyl)-4,5,6,7-tetrahydro-1-benzothien-2-yl]-2-ethylbutamide, Skyrin and NNC 250926. The absorption, dosage, catabolism, excretion and medicinal chemistry of these agents are the subject of this review. It emphasizes the role of glucagon in glucose homeostasis and how it could be applied as a novel tool for the management of diabetes mellitus by blocking its receptors with either monoclonal antibodies, peptide and non-peptide antagonists or gene knockout techniques.
    The Open Medicinal Chemistry Journal 12/2014; 8(1):28-35. DOI:10.2174/1874104501408010028
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    ABSTRACT: L-Deprenyl and its major metabolites were subjected to reversed-phase high-performance liquid chromatography (HPLC). The separation was monitored using both ultraviolet (UV) and electrochemical detectors. Ultraviolet absorbance detected L-deprenyl, L-nordeprenyl, L-methamphetamine, and L-amphetamine. Amperometric detection was specific and sensitive to the parent compound (L-deprenyl, a tertiary amine) only. Peaks of the major L-deprenyl metabolites did not give any comparable signal using amperometric monitoring.
    Acta Chromatographica 12/2014; 26(4):649–656. DOI:10.1556/AChrom.26.2014.4.7 · 0.49 Impact Factor
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    ABSTRACT: Neuroinflammation (NI) contributes to the pathogenesis of several neurodegenerative disorders. Epidemiological and a few animal studies have shown that chronic exposure of organophosphorus compounds (OPC) may cause neuronal injury and predispose to neuro- as well as psychotic disorders in conjunction with NI. However, in vivo studies are meager and do not represent the entire toxicologically diversified OPC. The present study aimed to investigate the effect of a highly toxic OPC, terbufos sulfone (TBS), on the status of proinflammatory cytokinesinterleukin-1β, interleukin-6 and tumor necrosis factor-α in adult's rats' brain. In addition, lactate dehydrogenase, nitric oxide and reduced glutathione were determined in brain homogenates. Red blood cell acetylcholinesterase was measured weekly. Sub-chronic, no-observable adverse effect level dose was employed. Four groups were setup - saline control, diabetes control, non-diabetes TBS and diabetes treated groups. Control groups received saline and the experimental groups were injected with TBS intraperitonealy for fifteen days daily. Twenty four hours after the last injection, the animals were euthanized to collect brain and serum samples. The study showed significant elevation of interleukin-6,tumor necrosis factor-α and lactate dehydrogenase in brain homogenates of TBS treated groups, while the presence of interleukin-1βwas significantly greater in the non-diabetes TBS treated group when compared with saline control. The increase was observed to be independent of acetylcholinesterase level and diabetes condition. The change in reduced glutathione was modest as compared with control. Based on the findings, the study concludes that the no-observable adverse effect level dose of TBS has potential to cause NI and subsequent neurodegeneration, a remarkable sign of many chronic neuronal and psychotic disorders. Further studies with prolonged exposure and other neurodegenerative parameters are warranted.
    CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 10/2014; 13(8). DOI:10.2174/1871527313666141023142539 · 2.70 Impact Factor
  • Ernest Adeghate, Erzsébet Fehér, Huba Kalász
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    ABSTRACT: Introduction: The worldwide number of patients suffering from diabetes mellitus (DM) is projected to approach 552 million by the year 2030. As diabetic neuropathy (DN) is present in 8% of new diabetic patients at the time of diagnosis and occurs in ∼ 50% of all patients with established DM, the number of patients who will develop painful DN will also increase. The suboptimal efficacies of currently approved drugs have prompted investigators to develop new therapeutic agents for the management of painful DN.Areas covered: In this review, the authors present and elucidate the current status of drugs under investigation for the treatment of painful DN. A short synopsis of currently approved drugs is also given. Literature information and data analysis were retrieved from PubMed, the American Diabetes and Neurological Associations Websites and ClinicalTrials.gov. The keywords used in the search included: DM, DN, painful diabetic neuropathy.Expert opinion: In addition to treating the pain associated with DN, the actual causes of the disease should also be targeted for improved management. It is hoped that drugs which improve vascular blood flow, induce neural regeneration, reduce hyperglycemia, oxidative stress and inflammation can be more effective for the overall treatment of painful DN.
    Expert Opinion on Investigational Drugs 08/2014; 24(1). DOI:10.1517/13543784.2014.954033 · 5.43 Impact Factor
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    ABSTRACT: Incretins, such as glucagon-like peptide-1 (GLP)-1, have been shown to elevate plasma insulin concentration. The purpose of this study is to investigate the cellular and molecular basis of the beneficial effects of GLP-1. Normal and diabetic male Wistar rats were treated with GLP-1 (50 ng/kg body weight) for 10 weeks. At the end of the experiment, pancreatic tissues were taken for immunohistochemistry, immunoelectron microscopy and real-time polymerase chain reaction studies. Samples of blood were retrieved from the animals for the measurement of enzymes and insulin. The results show that treatment of diabetic rats with GLP-1 caused significant (P < 0.05) reduction in body weight gain and blood glucose level. GLP-1 (10(-12)-10(-6) M) induced significant (P < 0.01) dose-dependent increases in insulin release from the pancreas of normal and diabetic rats compared to basal. Diabetes-induced abnormal liver (aspartate aminotransferase and alanine aminotransferase) and kidney (blood urea nitrogen and uric acid) parameters were corrected in GLP-1-treated rats compared to controls. GLP-1 treatment induced significant (P < 0.05) elevation in the expression of pancreatic duodenal homeobox-1, heat shock protein-70, glutathione peroxidase, insulin receptor and GLP-1-receptor genes in diabetic animals compared to controls. GLP-1 is present in pancreatic beta cells and significantly (P < 0.05) increased the number of insulin-, glutathione reductase- and catalase-immunoreactive islet cells. The results of this study show that GLP-1 is co-localized with insulin and seems to exert its beneficial effects by increasing cellular concentrations of endogenous antioxidant genes and other genes involved in the maintenance of pancreatic beta cell structure and function.
    Cell and Tissue Research 08/2014; DOI:10.1007/s00441-014-1959-9 · 3.33 Impact Factor
  • H. Kalasz, E. Adeghate, K. Tekes
    Digestive Diseases and Sciences 08/2014; 59(8):1657-1657. · 2.55 Impact Factor
  • E. Adeghate, M. Lotfy, J. Singh
    Digestive Diseases and Sciences 08/2014; 59(8):1648-1648. · 2.55 Impact Factor
  • Digestive Diseases and Sciences 08/2014; 59(8):1666-1666. · 2.55 Impact Factor
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    ABSTRACT: Abstract Context: Hypoxia injury (HI) with its long-term neurological complications is one of the leading causes of morbidity and mortality in the world. Currently, the treatment regimens for hypoxia are aimed only at ameliorating the damage without complete cure. The need, therefore, for novel therapeutic drugs to treat HI continues. Objective: This study investigates the protective effects of the ethanol extract of Cyperus rotundus L. (Cyperaceae) (EECR), a medicinal plant used in Ayurvedic traditional medicine against sodium nitrite-induced hypoxia in rats. Materials and methods: We have evaluated the protective effect of 200 and 400 mg/kg of EECR against sodium nitrite-induced hypoxia injury in rats by assessing the cognitive functions, motor, and behavioral effects of EECR treatment along with the histological changes in the brain. By comparing the protective effects of standard drugs galantamine, a reversible cholinesterase inhibitor and pyritinol, an antioxidant nootropic drug against sodium nitrite-induced hypoxia in rats, we have tested the protective ability of EECR. Results: EECR at doses of 200 and 400 mg/kg was able to protect against the cognitive impairments, and the locomotor activity and muscular coordination defects, which are affected by sodium nitrite-induced hypoxia injury in rats. Conclusion: Based on our results, we suggest that the medicinal herb C. rotundus possesses a protective effect against sodium nitrite-induced hypoxia in rats. Further studies on these protective effects of EECR may help in designing better therapeutic regimes for hypoxia injury.
    Pharmaceutical Biology 07/2014; 52(12):1-12. DOI:10.3109/13880209.2014.908395 · 1.34 Impact Factor
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    ABSTRACT: Glucagon-like peptide 1 (GLP-1) agonists are promising therapeutic agents in the treatment of diabetes mellitus. This study examines the mechanism of the protective effects of exenatide in experimental diabetes employing four groups of 10 rats each, in which two groups were streptozotocin-induced diabetic and two were control groups. One control and one diabetic group were treated with exenatide (1 µg/kg body weight) for 10 weeks. Blood plasma was taken for biochemical analyses while pancreatic tissue was taken for immunofluorescence and immunoelectron microscopy studies and real-time polymerase chain reaction for the expression of genes. The results show that exenatide improved body weight gain and reduced blood glucose in diabetic rats compared to control. Similarly, exenatide enhanced insulin release from pancreatic fragments and improved liver and kidney functions and lipid profile in diabetic rats compared to control. Exenatide not only induced significant increases in serum insulin level, but it also elevated the number of insulin-, GLP-1- and exenatide-positive cells compared to untreated control. Exenatide also elevated the number of catalase- and glutathione reductase-positive cells in diabetic rat pancreas compared to control. Exenatide caused significant elevation in the gene expressions of pancreatic duodenal homeobox-1, heat shock protein-70, glutathione peroxidase, insulin receptor and glucagon-like peptide-1 receptor in the pancreas of both control and diabetic rats compared to untreated animals. The results have demonstrated that exenatide can exert its beneficial and protective effects by elevating the levels of endogenous antioxidants and genes responsible for the survival, regeneration and proliferation of pancreatic beta cell.
    Journal of Endocrinology 12/2013; DOI:10.1530/JOE-13-0426 · 3.59 Impact Factor
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    ABSTRACT: Selegiline [(-)-deprenyl] is used to treat patients with Parkinson's disease. Nevertheless, in much higher doses it has beneficial effects in depression, and dementia of the aged patients. Selegiline undergoes a complex metabolic pathway. Its major metabolites include desmethylselegiline, (-)-methamphetamine and (-)-amphetamine, selegiline-N-oxide and formaldehyde as a small metabolic fragment in animal experiments. In addition, more than 40 minor metabolites of selegiline have also been either detected or proposed by investigators and researchers. This review analyses the pharmacological activity, generation pathway and the detection method of the major metabolites of selegiline.
    Current Medicinal Chemistry 12/2013; DOI:10.2174/0929867321666131218094352 · 3.85 Impact Factor
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    ABSTRACT: There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure to paraoxon (POX), an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined. Each rat was injected with 100 nmol of POX 5 days per week for 6 weeks. Blood glucose levels and red blood cell acetylcholinesterase activity were measured weekly. Biochemical analysis and morphological studies were performed at the end of the experiment. The results revealed that POX neither induces nor exacerbates diabetes mellitus in experimental rats. Liver and kidney/body weight ratios revealed statistically insignificant differences when compared with controls. Biochemical analysis of urine samples showed a small but not significant increase in protein level in all groups. Urine bilirubin was significantly higher in the diabetes + POX group when compared with the control group. The number of blood cells in urine was significantly higher in the POX-treated group compared with the control group. Hyperglycemia was noted in the diabetes and diabetes + POX groups, but neither in the saline control nor in POX-treated normal rats. Electron microscopy of POX-treated pancreas did not show any morphological changes in beta cells. These results suggest that POX does not cause diabetes mellitus at sub-lethal sub-chronic exposure. Copyright © 2012 John Wiley & Sons, Ltd.
    Journal of Applied Toxicology 10/2013; 33(10). DOI:10.1002/jat.2794 · 3.17 Impact Factor
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    ABSTRACT: Authorities of Drug Administration in the United States of America approved about 5000 drugs for use in the therapy or management of several diseases. About two hundred of these drugs have active metabolites and the knowledge of their medicinal chemistry is important both in medical practice and pharmaceutical research. This review gives a detailed description of the medicinal chemistry of drugs with active metabolites generated after conjugation. This review focused on glucuronide-, acetyl-, sulphate- and phosphate-conjugation of drugs, converting the drug into an active metabolite. This conversion essentially changed the lipophilicity of the drug.
    Mini Reviews in Medicinal Chemistry 10/2013; 13(11):1550-63. · 3.19 Impact Factor
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    ABSTRACT: Water-pipe smoking (WPS) is a common practice in the Middle East, and is now gaining popularity in Europe and USA. However, there is a limited number of studies on the respiratory effects of WPS. More specifically, the underlying pulmonary pathophysiologic mechanisms related to WPS exposure are not understood. Presently, we assessed the respiratory effects of nose-only exposure to mainstream WPS generated by commercially available honey flavored ``moasel`` tobacco. The duration of the session was 30 min/day and 5days/week for 1 month. Control mice were exposed to air only. Here, we measured in BALB/c mice the airway resistance using forced oscillation technique. Lung inflammation was assessed histopathologically and by biochemical analysis of bronchoalveolar lavage (BAL) fluid and oxidative stress was evaluated biochemically by measuring Lipid peroxidation, reduced glutathione and several antioxidant enzymes. Pulmonary inflammation assessment showed an increase in neutrophil and lymphocyte numbers. Likewise, airway resistance was significantly increased in WPS group compared to controls. Tumour necrosis factor α and interleukin 6 concentrations were significantly increased in BAL fluid. Lipid peroxidation in lung tissue was significantly increased whereas the level and activity of antioxidants including reduced glutathione, glutathione S transferase and superoxide dismutase were all significantly decreased following WPS exposure, indicating the occurrence of oxidative stress. Moreover, carboxyhemoglobin levels were significantly increased in the WPS group. We conclude that one-month nose-only exposure to WPS significantly increased airway resistance, inflammation and oxidative stress. Our results provide mechanistic explanation for the limited clinical studies which reported the detrimental respiratory effects of WPS.
    Journal of Applied Physiology 07/2013; 115(9). DOI:10.1152/japplphysiol.00194.2013 · 3.43 Impact Factor
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    ABSTRACT: Nociceptinergic system has become an important target for drug development since the identification of the "orphan", opioid-like-1 receptor and the isolation of its endogenous agonist nociceptin. Involvement of nociceptinergic system has been verified in a wide range of pathophysiological processes. A large number of nociceptinergic agonists and antagonists with peptide and non-peptide structures were developed. Several non- peptide nociceptinergic antagonists were recently shown effective in different animal models of parkinsonism. Neuropharmacological background for antiparkinsonian effect of nociceptinergic antagonists, experimental models with high predictive value, nociceptinergic antagonists shown to have potential effect in Parkinson's disease are summarized. Medicinal chemistry data (logP and TPSA) of the NOP receptor antagonists found effective in animal models of Parkinson's disease are provided.
    Mini Reviews in Medicinal Chemistry 05/2013; DOI:10.2174/13895575113139990006 · 3.19 Impact Factor

Publication Stats

2k Citations
395.84 Total Impact Points

Institutions

  • 1996–2015
    • Emirates University
      Arab, Alabama, United States
    • United Arab Emirates University
      • • Department of Anatomy
      • • Department of Pharmacology and Therapeutics
      • • Department of Pathology
      • • Department of Physiology
      Al Ain, Abu Dhabi, United Arab Emirates
  • 2004–2009
    • University of Central Lancashire
      • School of Forensic and Investigative Sciences
      Preston, ENG, United Kingdom
  • 1990–2002
    • Semmelweis University
      • Department of Anatomy, Histology and Embryology
      Budapeŝto, Budapest, Hungary
  • 1997–1998
    • Uzsoki Hospital
      Budapeŝto, Budapest, Hungary