Ernest Adeghate

Emirates University, Arab, Alabama, United States

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Publications (202)411.5 Total impact

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    ABSTRACT: The prevalence of diabetes mellitus (DM) is about 6 % across the globe. This prevalence has been reported to increase in the near future. This means that the number of women with DM who would like to get pregnant and have children will also increase. The present study is aimed at investigating the morphological changes observed in the uterus after the onset of DM. The study also examined the pattern of distribution of nociceptin (NC), a neuropeptide involved in the regulation of pain, a major physiological factor during parturition. The study shows a severe atrophy of uteri as early as 15 days post DM and continued until the termination of the eight-week study. This atrophy was confirmed by light microscopy. Electron microscopy study showed atrophy of the columnar cells of the endometrium, reduced myofibril number and destruction of smooth muscle cells in the myometrium of diabetic rats compared to control. Immunofluorescence and immunoelectron microscopy studies clearly demonstrated the presence of NC in the endometrium, myometrium and on the myofibrils of the smooth muscles of both control and diabetic rat uteri. In addition, NC-positive neurons and varicose fibres were observed in the myometrium of both normal and diabetic rats. However, the expression of NC decreased after the onset of DM. Morphometric analysis showed that the number of NC-labeled cells was significantly (p < 0.05) lower in diabetic rat uteri compared to those of control. In conclusion, DM-induced uterine atrophy is associated with a decrease in the expression of NC in cells, neurons and myofibrils of the rat uterus.
    No preview · Article · Nov 2015 · Journal of Molecular Histology
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    ABSTRACT: Introduction: Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 350 million people worldwide. Also, another one billion people in the world are pre-diabetic, who may eventually end up with full- blown diabetes. It costs around 1,200 billion USD to diagnose, treat and care for both type 1 DM (T1DM) and type 2 DM (T2DM) patients globally. The disorder is rapidly increasing out of proportion in both developed and developing countries, especially T2DM, which is associated with modern lifestyle habits such as reduced physical activity, diet, obesity and genetic factors. If left untreated, DM can lead to a number of diseases and long-term complications leading subsequently to death. Areas covered: In this mini review, we aim to highlight a number of complications, cascades or pathways (polyol, hexosamine, protein kinase C, advanced glycation-end product) of events and cellular, sub-cellular and molecular mechanisms associated with DM-induced hyperglycaemia. Conclusion: Chronic complications of DM are caused largely by HG-induced cellular and molecular impairment of neural and vascular structure and function. HG-induced oxidative stress is a major contributor in the development of long-term complications of DM. DM-induced neuropathy and angiopathy, in turn, may lead to the dysfunction of cells, tissues and organ systems.
    No preview · Article · Oct 2015 · Current diabetes reviews
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    ABSTRACT: Background/Aim: Type 2 diabetes is the most common metabolic disorder, characterized by insulin resistance and pancreatic islet beta-cell failure. The most common complications associated with type 2 diabetes are hyperinsulinemia, hyperglycemia, hyperlipidemia, increased inflammatory and reduced insulin response. Aspirin (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with the prevention of diabetes, obesity and related cardiovascular disorders. Aspirin has been used in many clinical and experimental trials for the prevention of diabetes and associated complications. Methods: In this study, five month old Goto-Kakizaki (GK) rats, which showed signs of mild hyperglycemia (fasting blood glucose 80-95 mg/dl vs 55-60 mg/dl Wistar control rats) were used. Two subgroups of GK and Wistar control rats were injected intraperitoneally with 100 mg aspirin/kg body weight/ day for 5 weeks. Animals were sacrificed and blood and tissues were collected after performing glucose tolerance (2 h post 2g IP glucose ingestion) tests in experimental and control groups. Results: Aspirin caused a moderate decrease in hyperglycemia. However, we observed a significant improvement in glucose tolerance after ASA treatment in GK rats compared to the nondiabetic Wistar rats. Also, the ASA treated GK rats exhibited a significant decrease in insulinemia. ASA treatment also caused a marked reduction in the pro-inflammatory prostaglandin, PGE2, which was significantly higher in GK rats. On the other hand, no significant organ toxicity was observed after ASA treatment at this dose and time period. However, the total cholesterol and lipoprotein levels were significantly increased in GK rats, which decreased after ASA treatment. Immunofluorescence staining for insulin/glucagon secreting pancreatic cells showed improved beta-cell structural and functional integrity in ASA-treated rats which was also confirmed by SDS-PAGE and Western blot analysis. Conclusion: The improved glucose tolerance in ASA-treated GK rats may be associated with increased insulin responses due to the anti-inflammatory properties of ASA and enhanced nitric oxide (NO) level which facilitated insulin signaling and energy utilization in target tissues. These results may have implications in determining the therapeutic use of ASA in insulin-resistant type 2 diabetes.
    No preview · Article · Jul 2015 · Cellular Physiology and Biochemistry
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    Salem KA · Jacobson M · Shafiullah M · Oz M · Adeghate E · Howarth FC

    Full-text · Article · May 2015
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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.
    No preview · Article · May 2015 · Pancreas
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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.
    Full-text · Article · Mar 2015
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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.
    No preview · Article · Feb 2015 · Journal of Applied Toxicology
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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.
    No preview · Article · Jan 2015 · Pharmaceutical Biology
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    Full-text · Article · Jan 2015

  • No preview · Article · Jan 2015
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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.
    Full-text · Article · Dec 2014 · The Open Medicinal Chemistry Journal
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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.
    No preview · Article · Dec 2014 · Acta Chromatographica
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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.
    No preview · Article · Oct 2014 · CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders)
  • 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 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.
    No preview · Article · Aug 2014 · Expert Opinion on Investigational Drugs
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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.
    Full-text · Article · Aug 2014 · Cell and Tissue Research
  • H. Kalasz · E. Adeghate · K. Tekes

    No preview · Article · Aug 2014 · Digestive Diseases and Sciences
  • E. Adeghate · M. Lotfy · J. Singh

    No preview · Article · Aug 2014 · Digestive Diseases and Sciences

  • No preview · Article · Aug 2014 · Digestive Diseases and Sciences
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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.
    No preview · Article · Jul 2014 · Pharmaceutical Biology
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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.
    Full-text · Article · Dec 2013 · Journal of Endocrinology

Publication Stats

3k Citations
411.50 Total Impact Points


  • 1996-2015
    • Emirates University
      Arab, Alabama, United States
    • United Arab Emirates University
      • • Department of Anatomy
      • • Department of Pharmacology and Therapeutics
      • • Department of Physiology
      • • College of Medicine and Health Sciences
      Al Ain, Abu Dhabi, United Arab Emirates
  • 1994-2004
    • University of Central Lancashire
      • School of Forensic and Investigative Sciences
      Preston, England, United Kingdom
  • 1998
    • Emirates Aviation College
      Dubayy, Dubai, United Arab Emirates
  • 1997
    • Uzsoki Hospital
      Budapeŝto, Budapest, Hungary
  • 1990-1991
    • Semmelweis University
      • Department of Anatomy, Histology and Embryology
      Budapeŝto, Budapest, Hungary