Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 7th Euro-Global Summit on Toxicology and Applied Pharmacology Rome, Italy.

Day 2 :

Keynote Forum

Silvio De Flora

University of Genoa, Italy

Keynote: Modulation of cigarette smoke lung carcinogenesis. The experimental background

Time : 10:00-10:30

Conference Series Euro Toxicology 2016 International Conference Keynote Speaker Silvio De Flora photo
Biography:

Silvio De Flora, MD, PhD, was Assistant Professor (1966), full Professor and Chairman (1975), and Professor Emeritus (2012) at the School of Medicine of the University of Genoa (Italy), where he was director for 22 years of the Institute of Hygiene and Preventive Medicine (1986-1998) and of the Department of Health Sciences (1999-2005 and 2010-2012). Author of 460 full length papers, 308 of which available in PubMed. The overall impact factor is 1500. With almost 14,000 citations, the h-index is 58. He published in collaboration with 140 laboratories in European countries, China, Japan, India, New Zealand and USA. Member of the editorial board of 16 international journals. Principal investigator of a number of research projects, 10 of which awarded by the US NIH. He received several honors, among which the award from the Michigan State University (2002), the Sobels Award (Greece, 2005), and dedication of 10th ICMAA (Brazil, 2010).

Abstract:

Although cigarette smoke (CS) is recognized to play a dominant role in the epidemiology of lung cancer, cancer at other sites, and a variety of chronic degenerative diseases, it is difficult to reproduce its carcinogenicity in experimental test systems. We have developed an animal model that is suitable to detect the induction of lung tumours and other histopathological alterations induced by mainstream CS (MCS). This model, which involves the whole-body exposure of Swiss H mice to MCS during the first 4 months of life, followed by 3-4 months in filtered air, was validated by evaluating a number of dietary and pharmacological agents. The agents were administered orally, either individually or in combination, under conditions mimicking interventions either in current smokers or ex-smokers or even reproducing a transplacental chemoprevention. They included anti-inflammatory drugs, such as glucocorticoids (budesonide) and NSAIDs inhibiting COX-1, COX-2 and/or 5-LOH (celecoxib, aspirin, naproxen, licofelone), antidiabetic drugs (metformin, pioglitazone), antineoplastic agents (lapatinib, bexarotene, vorinostat), and natural products and dietary supplements (phenethyl isothiocyanate, myo-inositol, N-acetylcysteine, ascorbic acid, berry extracts). In addition, we evaluated a number of agents for the ability to affect molecular biomarkers in the same mouse model or in rats exposed either to MCS or to environmental CS (ECS). The results obtained provide evidence that experimental studies evaluating lung tumours and/or molecular alterations may be useful, together with epidemiological data, to assess modulation of lung carcinogenesis in smokers, to predict both safety and efficacy of putative lung cancer chemopreventive agents, and to explore their mechanisms of action.

Keynote Forum

Yiqun Deng

South China Agricultural University, China

Keynote: Mitochondrial biogenesis protects animal cells from T-2 toxin

Time : 08:55-09:20

Conference Series Euro Toxicology 2016 International Conference Keynote Speaker Yiqun Deng photo
Biography:

Yiqun Deng completed his Doctorate degree in Biochemistry and Molecular Biology at Zhongshan School of Medicine, Sun Yat-Sen University in 2002. After five years’ Post-doctoral research at Weill Medical College, Cornell University, he is currently working as Professor, Dean of the College of Life Sciences, South China Agricultural University and Director of Guangdong Provincial Key Laboratory of protein function and regulation in agricultural organisms. He has authored 40 publications in peer-reviewed journals. He is an active member in five scientific societies and serves as an Editorial Board Member of several scientific journals.

Abstract:

T-2 toxin is one of the most toxic mycotoxins, which has broad toxic effects, like apoptosis, cell cycle arrestment and protein synthesis inhibition. However, the protective responses of the cells to T-2 toxin remain unclear. In our study, it was shown that T-2 toxin strongly induced the ROS accumulation, DNA damage and apoptosis in chicken primary hepatocytes. To further clarify the molecular mechanisms of the toxic and anti-toxic actions, the proteomic changes of chicken primary hepatocytes upon T-2 toxin treatment were investigated, and it was shown that the most abundant proteins regulated by T-2 toxin were associated with cell redox homeostasis, which explained its property of ROS accumulation. Surprisingly, 34% of the T-2 toxin regulated proteins were located in the mitochondrion, and particularly, most of them were up-regulated, which suggest that T-2 toxin potentially impacts on mitochondrial biogenesis. We confirmed experimentally that T-2 toxin enhanced the mitochondrial biogenesis and which generally occurred in different cells including HeLa, HepG2 and HEK 293-T, besides chicken primary hepatocytes. Subsequently, it is found that one of the key regulator of mitochondrial biogenesis, SIRT1, was upregulated under T-2 toxins treatment, and the enhancement of mitochondrial biogenesis and cell viability under T-2 toxin treatment were impaired by knocking-down SIRT1, and strengthened in SIRT1-overexpression cells. Interestingly, the promoter region of SIRT1 is not responsible for the up-regulation by T-2 toxin and further investigation is under way. In summary, our study suggested that the mitochondrial biogenesis enhancement via SIRT1 plays an important role in the protective response to T-2 toxin. This might provide a new direction in T-2 toxin defense.

Keynote Forum

Giovanni Pagano

Federico II Naples University, Italy

Keynote: Rare earth elements as novel environmental contaminants: current knowledge and research priorities

Time : 10:30-11:00

Conference Series Euro Toxicology 2016 International Conference Keynote Speaker Giovanni Pagano photo
Biography:

Giovanni Pagano graduated in Biological Sciences in 1971 at Naples University and at the International Institute of Genetics and Biophysics in Naples. He served the Italian National Cancer Institute in Naples up to retirement in 2005, with a major focus on environmental toxicology. In recent years GP has collaborated with a number of national and international institutions, and lecturing at several post-graduate courses. The current positions are Research Contractor at Federico II University, and Associate Researcher at the Stazione Zoologica Anton Dohrn. GP authored over 100 publications receiving over 2000 citations; ResearchGate Score 36.63.

Abstract:

Rare earth elements (REEs) are used in several industrial and medical applications. Relatively scarce information is available to date on REE-associated biological effects, including bioassays on animal models, and human health effects following occupational or environmental REE exposures. The literature is mostly confined to reports on cerium, lanthanum and gadolinium, whereas information gaps persist on the health effects of other REEs. An established action mechanism in REE-associated health effects relates to modulating oxidative stress, and adverse effects include a number of endpoints, such as growth inhibition, cytogenetic effects, embryonic arrest and malformations, and organ-specific toxicity. A major role for REE-associated effects relates to pH-dependent REE speciation, and environmental acidification enhances REE toxicity.

We have reported recently that a set of light REEs [Y(III), La(III), Ce(III), Nd(III), Sm(III) and Gd(III)] induce a number of adverse effects to early life stages in sea urchin sperm and embryos, including developmental defects, cytogenetic damage and redox anomalies. The current study is focused on some heavy REEs [Dy(III), Ho(III), Er(III), Yb(III) and Lu(III)], altogether pointing to more severe effects vs. light REEs. The likely environmental threats arising from REE exposures deserve a new line of research efforts. Research priorities should focus on elucidating the comparative toxicities of heavy vs. light REEs, which might provide warning about the use of most toxic REEs. Most relevant research lines should be designed in mammalian and human exposures, namely by performing life-long exposures in animal model and by undertaking appropriate epidemiologic investigations.

Keynote Forum

Wei Zheng

Purdue University, USA

Keynote: Role of altered adult neurogenesis in manganese-induced Parkinsonian disorder

Time : 09:30-10:00

Conference Series Euro Toxicology 2016 International Conference Keynote Speaker Wei Zheng photo
Biography:

Dr. Zheng received his Ph.D. from University of Arizona in Tucson. He was an assistant professor (1993-2000) and later associate professor (2000-2003) at Columbia University in New York city. Dr. Zheng joined Purdue University in 2003 and became a full professor in 2006. He has been serving as the Head of School of Sciences since 2008. Dr. Zheng has published one book, 161 peer-reviewed papers and more than 220 meeting proceedings and abstracts. He is a Fellow of the U.S. Academy of Toxicological Sciences and a frequet reviewer for NIH study sections and for more than 40 research journals.

Abstract:

Neural stem/progenitor cells (NSPCs) in the adult subventricular zone (SVZ) have the capability to self-renew and to migrate via the rostral migratory stream (RMS) to reach their final destination, the olfactory bulb (OB), where they mature and integrate into the local neuronal circuitry. Adult neurogenesis plays an important role in the etiology of neurodegeneratieve diseases. This study was designed to determine if exposure to toxic metal manganese (Mn) disturbed the proliferation, migration, survival and differentiation of NSPCs from SVZ via RMS to OB. Adult rats received a single ip-dose of BrdU at the end of 4-wk Mn exposure to label proliferating cells. Immunostaining and cell-counting showed a 48% increase of BrdU(+) cells in Mn-exposed SVZ than in controls (p<0.05). The BrdU(+) proliferating cells were identified as a mixed population of GFAP(+), Nestin(+) and DCX(+) cells, representing type-B neural stem cells, type-C transit progenitor cells, and migratory neuroblasts, respectively. Another group of adult rats received 3 daily ip-injections of BrdU followed by Mn exposure. By 4-wk post-BrdU labeling, most surviving BrdU(+) cells in the OB were differentiated into NeuN(+) matured neurons. However, survival rates of BrdU/NeuN/DAPI triple-labeled cells in the OB were 33% and 64% in Mn-exposed and control animals, respectively (p<0.01). These results suggest that Mn exposure initially enhances the cell proliferation in adult SVZ mainly by increasing type-B cells. In the OB, however, Mn exposure significantly reduces the surviving adult-born cells and markedly inhibits their differentiation into mature neurons, resulting in an overall decreased adult neurogenesis in the OB.  (Up to 250 words)

Keynote Forum

May Azzawi

Manchester Metropolitan University, UK

Keynote: The nanotoxicological influence of nanoparticles on vascular function

Time : 11:30-12:00

Conference Series Euro Toxicology 2016 International Conference Keynote Speaker May Azzawi photo
Biography:

Dr. May Azzawi is a Reader in Vascular Physiology at the Healthcare Science Research Institute (Faculty of Science and Engineering), Manchester Metropolitan University, United Kingdom. She received her PhD from the University of London (National Heart and Lung Institute, Royal Brompton Hospital, London) and has held postdoctoral and fellowship positions at the University of Manchester. She has over 20 years’ research experience in multidisciplinary fields, including Vascular Physiology and Nanomedicine, and has published widely (> 3,000 citations to date). Dr. Azzawi leads a ‘Nanovascular’ research group investigating the influence of nanoparticles on cellular and vascular function using ex vivo and 3D in vitro models. Her group focus on strategies (Nutraceutical and Nanotechnology) for the preservation and restoration of vascular function. She has authored over 50 publications, including peer reviewed articles and book chapters, and has secured over half a £million in research funding (Innovate UK, Erasmus Mundus, EPSRC). She is co- editor of the journal ‘Regenerative Nanomedicine’; editorial board member of ‘Applied Nanostructured Materials’; she co-chaired the 3rd International conference on Nanotechnology in Medicine; and acts as referee for a number of international journals in the fields of Nanomedicine and Vascular Science.

Abstract:

Silica nanoparticles (SiNPs) are attractive drug delivery platforms and diagnostic tools, however, recent reports suggest that they may be detrimental to arterial function. We aimed to examine whether SiNPs influence the function of small size arteries, which play an essential role in controlling blood perfusion into tissues. We show that while exposure to SiNPs under static conditions, attenuated dilator responses ex vivo, attenuation was only evident at lower agonist concentrations, when exposed under flow conditions or after intravenous injection, in vivo. Pharmacological inhibition studies suggest that SiNPs may interfere with the endothelial dependent hyperpolarising factor (EDHF) vasodilator pathway. The dosage dependent influence of SiNPs on arterial function, demonstrated in our study, will help identify strategies for their safe clinical administration in the future.

Conference Series Euro Toxicology 2016 International Conference Keynote Speaker Swamy KB photo
Biography:

Abstract:

Background: Diabetes Mellitus type 2 is a chronic metabolic disorder which is rapidly increasing in incidence globally. The International Diabetes Federation (IDF) reports that as of 2013 there were more than 382 million people living with diabetes. As the currently available anti-diabetic treatment modalities have not been meeting the requirements there is a dire need to identify a more number of safe and effective anti-diabetic agents. The aim of this study was to identify the effectiveness of Synsepalum dulcificum fruit (Miracle Fruit) extract in reducing blood glucose levels in Streptozotocin (STZ)-Nicotinamide (Nam) induced diabetic rats.
Methods: In this experimental research 29 Sprague-Dawley (SD) rats were divided into groups (G) 1. Normal controls -6 rats and group (G)2. Streptozotocin -Nicotinamide induced diabetic -23 rats. Again these 23 SD rats were divided into 4-groups as- G1.Diabetic controls-5, G2.Glibenclamide (600 µg/kg)-treated-6, G3. Medium dose fruit extract (250 mg/kg) treated-6 and G4. High dose fruit extract (500 mg/kg) treated-6.  All rats were assessed for fasting blood glucose and body weights every week during the span of 21 days period of study. Before starting the experimental research the body weights and fasting blood glucose were measured for all the rats. Then the toxicity of the fruit extract was tested with the highest dose of 5000 mg/kg on 12 SD rats and it showed that no adverse effects at all on the rats’ health.
Results: Eventually this study revealed that high dose fruit extract (500 mg/kg) only could significantly reduce fasting blood glucose levels (p<0.001) even though it caused a slight increase in body weight. Conclusion This study revealed that Synsepalum dulcificum fruit (Miracle Fruit) extract shows acceptable anti-hyperglycemic effects in rats. (Please refer to my article published: “The Clinical Effects of Synsepalum Dulcificum- A Review: J Med Food 17(11) 2014 1165 1169).

Conference Series Euro Toxicology 2016 International Conference Keynote Speaker Hemant Misra photo
Biography:

Dr. Hemant Misra received his PhD from Lucknow University in Medicinal and Pharmaceutical Chemistry and has published over 65 articles and a patent. He is VP Clinical Development for Prolong Pharmaceuticals. Dr. Misra has over 30 years of biopharmaceutical development, global clinical study management and corporate development experience. Dr. Misra has managed drug development, CGMP manufacturing, CTM, quality systems and multiple global clinical trials.

Abstract:

A 13-week study was conducted in Sprague Dawley rats and cynomolgus primates to assess the safety and pharmacokinetics of ANF-Rho as compared to Neulasta® (pegfilgrastim).  ANF-Rho is a novel polyethylene glycol-modified granulocyte colony stimulating factor that has biophysical and biological properties that produce a distinct pharmacokinetic and pharmacodynamic profile as compared to pegfilgrastim (Neulasta®).
The study design used 288 rats, divided into 5 dosage groups: control, 100, 300, 1000 (high) and 1000 (positive) µg/kg. A total of 58 monkeys were also divided into 5 dosage groups: control, 75, 250, 750 (high dose) and 750 (positive) µg/kg of ANF-Rho.   Doses were administered by weekly subcutaneous injections on Day 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85 and 92 at a dose volume of 5 mL/kg for rats and 2mL/kg for primates.  Genotoxicity assessments were evaluated using Salmonella typhimurium and Escherichia coli reverse mutation assay, rodent blood micronucleus assay and chromosomal aberration assay. Toxicology assessment included clinical observations, body weight change, food consumption, ophthalmic examination, function observational battery (motor activity, behavioral changes, coordination and sensory/motor reflex response), organ weight, bioanalytical and toxicokinetic analysis, immunogenicity, gross necropsy and histopathology.
No observed clinical signs seemed to be related to ANF-Rho administration.  There were no related effects in body weight changes or food consumption.  Observed ophthalmic effects were considered procedural-related due to the low incidence.  No biologically meaningful findings were noted during the function observational battery assessment.  Preliminary analysis showed a dose-related increase in spleen weight in rats and a dose-dependent decrease in kidney weight in primates.  Genotoxicity studies found no signs of mutagenicity, clastogenicity or cytotoxicity.
The results from this preliminary toxicology studies are unremarkable. These results are consistent with those of an earlier 28-day study.  Results from the 28-day rat neutropenia dosage model found that the blood pharmacodynamics parameters of ANF-Rho were significantly superior to Neulasta.  Both PK and PD data demonstrate relatively predictable systemic exposures and activity following SC or IV dose levels in both rat and primate. It is anticipated that this long terms 13-week study will provide evidence of safety sufficient to support advancement of ANF-Rho into Phase II clinical studies in chemotherapy-induced neutropenia.

  • Environmental Toxicology | Risk Assessment | Metal Toxicity
Location: Olimpica-2
Speaker

Chair

Marcelo L Larramendy

National University of La Plata, Argentina

Speaker

Co-Chair

May Azzawi

Manchester Metropolitan University, UK

Biography:

Lisa Vaccari has been the Leader of the SISSI infrared beamline at the Elettra Sincrotrone Trieste since 2006. She is an expert in Bio-spectroscopy and pioneere the exploitations of microfabrication capabilities for the design and fabrication of IR-suitable microfl uidic devices for performing in vitro bio-experiments under physiological conditions. She has experience in several other analytical techniques and she is actively involved in several projects in the fields of “Environmental toxicology, toxicology of nanomaterials, cellular toxicology of drugs and chemicals”.

Abstract:

The setting up of new methodologies for the assessment of material toxicology is a field of research continuously evolving in order to answer the new and urgent questions of the modern era. In this framework, SR-FTIRM is emerging as a valuable tool for in vitro and ex vivo toxicological studies. Th e technique is able to provide biochemical information on the sample under investigation in a label-free, safe and spatially-resolved manner, through the investigation of the vibrational motions of the molecular constituents. In this presentation, a short introduction of Elettra Sincrotrone Trieste, III generation Synchrotron
Facility in Italy will be given, focusing on the activities in the toxicology fi eld at SISSI beamline, the infrared laboratory at Elettra. Several topics will be covered, such as: Th e chemical characterization of asbestos bodies versus environmental particulates (anthracosis) in human lung tissues from asbestos exposed and control patients; the biochemical modifications on crustacean (Porcellio scaber) digestive glands upon exposure to diverse nanoparticles, (tungsten, zinc and silver oxides), the concentration of which in environmental systems is increasing as a consequence of anthropogenic activities. Th e correlation between chemical state, concentration and shape of the nanoparticles on animal toxicity will be highlighted and; an overview
on the in vitro capabilities of SR-FTIRM will be given, focusing on the possibility to monitor in real-time on live single cells the effects of therapeutics and stressor agents in general. A comparison with more conventional analytical approaches such as flow cytometry will be presented.

Gertie H P Arts

Alterra Wageningen University and Research Centre, The Netherlands

Title: Effects of linuron on a rooted aquatic macrophyte in sediment-dosed test systems

Time : 12:00-12:20

Biography:

Gertie H P Arts studied Biology at the Radboud University in Nijmegen, The Netherlands. She has completed her PhD in the Natural Sciences from the same
university. She works at Alterra as a Senior Scientist in the Environmental Risk Assessment team. She has a focus on aquatic macrophyte ecotoxicology and risk assessment. She has published more than 100 papers in reputed journals and reports, and is serving as an Editor for the Journal of Environmental Toxicology and Chemistry.
 

Abstract:

Effects of linuron on the sediment-rooted aquatic macrophyte Myriophyllum spicatum L. Were studied in sediment-dosed test systems following an OECD test guideline with extended test duration. Sediment, pore water, overlying water and macrophyte shoots were sampled weekly for chemical analyses. Linuron was stable in the sediments. Sediment and pore water concentrations were in equilibrium aft er 48 h. Overlying water concentrations increased over time, but did not reach equilibrium with pore water concentrations and were 1000 times lower. Mass balances showed a rapid uptake of linuron by macrophyte roots. Known pathways and the compound’s properties support the conclusion that Myriophyllum takes up linuron from pore water directly through the roots. Modeling supported the conclusions that high concentrations in the shoots could be explained by translocation of linuron by the roots to the shoots. The fluxes calculated for linuron support this interpretation.
At the experimental start, several pathways played a role, i.e. linuron fl uxes from pore water to overlying water and from pore water to roots. The flux from pore water to overlying water decreased later, while the translocation fl uxes from roots to shoots increased. Hence, eff ects on macrophytes in this type of sediment toxicity test should be expressed in terms of pore water concentrations. Sensitivity of water- and sediment-dosed test systems will be discussed in the light of compound properties.

Break: Lunch Break 12:20-13:05 @ Hotel Restaurants

Anna Magdalena Bogdali

Jagiellonian University Medical College in Krakow, Poland

Title: Nickel related Staphylococcus aureus infections in atopic dermatitis

Time : 13:05-13:25

Biography:

Anna Magdalena Bogdali graduated with her Master’s degree at the Department of Biochemistry, Biophysics and Biotechnology of Jagiellonian University in Krakow. She completed her PhD on Atopic Dermatitis from Jagiellonian University Medical College in Medical Biology. She participated in the Socrates/Erasmus and 6th and 7th Framework European Programs. She stayed in the Angioedema Hungarian Center at the Semmelweis University in Budapest and she is involved in projects on hereditary angioedema concerning genetic background and immune mechanisms at the Jagiellonian University Medical College in Krakow. Her interests are immune and genetics mechanisms mostly related to T cells in the skin and circulatory system.

Abstract:

Pollution of the air, water and food by metals results in changes of microbiota because metals are common enzymatic cofactors of bacterial cells. Concentration of nickel in the air in Krakow is approximately 20 ng/m3 in PM10. Nickel allergy is oft en found in patients with atopic dermatitis. Number of colonies of Staphylococcus aureus increases in acute phase and is reduced in remission of atopic dermatitis. Thus, it is believed that staphylococcal-derived infections exacerbate allergic inflammation. Nickel participates in virulence of Staphylococcus aureus and is required as a cofactor for bacterial enzymes
including urease that can regulate pH. It is still unknown whether nickel-sensitive urease can regulate pH of the skin changed in patients with atopic dermatitis. In our current studies, 85% of patients with atopic dermatitis is infected by difficult to treat infections by methicillin-resistant Staphylococcus aureus. Bacterial infections are initiated by specifi c adhesion of a bacterium
to the target environment. Staphylococcus aureus can attach to nickel nanostructures with dimensions comparable to the size of a single bacterium. Changes of cytokine milieu due to nickel action on T cells can increase number of immature Th 0 and it can also promote staphylococcal infections because it reduces bacterial clearance. Th us, more immature T cells less cellular immune
mechanisms protecting against staphylococcal infections. Therefore we believe that nickel allergy can promote Staphylococcus aureus infections in atopic dermatitis. All these studies are required to fully understand patho-mechanism of atopic dermatitis that is useful for more individual and consequently better treatment of patients.

Biography:

Zhi-Zhong Guan completed his PhD from Karolinska Institutet, Sweden in 1997. He is the Director of the Key Lab of the Endemic and Ethnic Diseases in Education Ministry of China. He has published more than 400 papers (including more than 100 SCI collected papers) in peer-reviewed journals and has been serving as an Editorial Board Member or reviewer of several journals.

Abstract:

Endemic fluorosis widely occurs in the world and is characterized by skeletal and dental fl uorosis and a vast array of pathological changes in whole bodies, which has been proved by our large number of basic investigations. Coal-burning type of endemic fl uorosis is the severest one, which was confi rmed in China in 1970’s. Th is type of endemic fluorosis is primarily induced by fl uoride-contaminated food and air indoor caused by smoke emitted during burning coal, which contains a high concentration of fl uoride. In China, about 36 millions of people live in such areas of coal-burning type of endemic flruosis. Among the population, 18 millions are suff ered from dental fl uorosis and 1.5 millions skeletal fl uorosis. Since 1980, an efficient strategy relating integrated control has been carried out for eliminating the disease in in China. After taking the measurement for many years, the adapted coal-burning stoves have been set up and the improve health education obtained in most of
families in the endemic fluorosis areas, which brings the signifi cant decline of fl uoride contamination on food and air indoor. The strategy has successfully resulted in a signifi cant decrease in the numbers of the patients with dental and skeletal fluorosis, and in a great improvement in health conditions of the people lived in the areas. At present, the coal-burning type of endemic fluorosis in China has been effi ciently controlled at present. Importantly, it is necessary to take a long-period of integrated control for effi ciently eliminating the hazard of coal-burning type of endemic fluorosis.

Biography:

Abstract:

Bioaccumulation of heavy metals has been reported to be common in leafy vegetables planted in gardens located at 20 meters away from traffi c-congested highways, automobile mechanic workshops and refueling service stations. Th is study assessed the level of some heavy metals in the leaves of fluted pumpkin (Telfairia occidentalis) planted at varying distances (10, 20, 30, 40 and 50 m) away from mega refueling service stations (MRSS) in three Southern Nigerian States. The leaves harvested aft er three months of planting were processed using standard procedures for heavy metals determination. Th e heavy metals (Pb, Ni, Mn, Cd, and Zn) were determined following standard atomic absorption spectrophotometric methods. The results showed that the levels of Pb, Cd and Ni accumulated in the leaves were signifi cant (p<0.05) between, but not within, the different distances. Also, the levels of the heavy metals recorded in these leaves followed the order: 10 m>20 m>30 m>40 m>50 m. However, the levels of these heavy metals in the leaves planted at 10 and 20 m away from MRSS were signifi cantly (p<0.05) higher, compared to the levels recorded for 30, 40 and 50 m, respectively. Th ese observations indicated that planting of Telfairia occidentalis leaves within 20 m distance from MRSS is likely to expose the leaves to the risk of heavy metals contamination and bioaccumulation and; the vegetables planted within this range from MRSS may be hazardous for human consumption. Therefore, it may be concluded that it is safer to cite farmlands for Telfairia occidentalis beyond 30 m from MRSS to reduce the rate of exposure to MRSS-related heavy metals contamination, and bioaccumulation of the heavy metals in the leaves.

Branko Petrinec

Institute for Medical Research and Occupational Health, Croatia

Title: 137Cs in soil and milk in the region of Zagreb, Croatia

Time : 14:05-14:25

Biography:

Branko Petrinec obtained his PhD degree from the Physics Department of the University of Zagreb. He is a Research Associate at the Institute for Medical
Research and Occupational Health in Zagreb, and an Assistant Professor at the Department of Physics of the Josip Juraj Strossmayer University in Osijek. He has published more than 20 papers in reputed journals. He was the President of the Scientific Committee of the Tenth Symposium of the Croatian Radiation Protection Association. In 2011, he was the Laureate of the CRPA Young Scientists Award.

Abstract:

At the Institute for Medical Research and Occupational Health in Zagreb, Croatia, research on environmental radioactivity has been carried out over a number of years. Aft er the Fukushima accident in March of 2011, we have paid a special attention to its possible impact on the radioactivity of soil and precipitation in Northwest Croatia (Zagreb region). Before and after the accident, we determined the activity concentrations of 137Cs (A) in soil samples taken from 3 adjacent surface layers (depths of 0-5 cm, 5-10 cm and 10-15 cm) as well as in samples of milk. Before the accident, A in the soil was nearly uniform, only slightly increasing with increasing depth. Shortly aft er the accident, we observed an increase of A in the topmost layer, which was in agreement with the values of A measured in fallout. In subsequent years, we have detected both the penetration of 137Cs deeper into the soil and the overall decrease in A. In 2010, the values of A in milk were quite uniform over the months, amounting to about 35 Bqm-3. In 2011, this increased to 199 Bqm-3 in average, mainly due to the large values measured in the summer months; we attribute this eff ect to the infl ux of the radioactive matter from Fukushima. In consequence of the increased presence of 137Cs, the estimated yearly eff ective dose due to the intake of 137Cs via milk in 2011 was 200 nSv, which
can be compared with 73 nSv in the period of 2010-2015.

Biography:

Walter Lichtensteiger has served as a Professor of Pharmacology and Toxicology at the University of Zurich, Switzerland, with teaching obligations at the Swiss Federal Institute of Technology (ETH), Zurich and after retirement, he founded the spin-off company GREEN Tox (Group for Reproductive, Endocrine and Environmental Toxicology) in 2005, together with Margret Schlumpf. GREEN Tox focuses on “Research and continuous education on environmental chemicals”. He is a member of several committees of the OECD programme for testing of chemicals.

Abstract:

Developmental exposure to polychlorinated biphenyls (PCBs), bisphenol A (BPA) or the pesticide chlorpyrifos (CPF) impairs hippocampus-dependent behaviors (learning) in adult off spring. In a search for shared eff ects on gene networks, we treated pregnant rats with PCB mixture Aroclor1254 (5, 0.5 mg/kg), BPA (5, 0.5 mg/kg), or CPF (3, 1 mg/kg) in the feed (PCB, BPA) or subcutaneously (CPF). Transcriptome analysis was done in hippocampus from off spring at postnatal day six (PND6) by NGS. In male hippocampus, analyses revealed common eff ects on genes regulating hippocampal development. At
behaviorally active doses, all chemicals showed upregulation of Gli3, neuregulin1, Erbb4, Sox6, Sox11, Pou2f2/Oct2, Pou3f2/ Brn2 and Wnt receptors Fzd3 and Fzd6. microRNA-24 was down-regulated, indicating possible interactions with posttranscriptional regulation of Sox6. Pou2f1/Oct1, Pou3f3/Brn1, Sox2 and Sox17 was aff ected by only two treatments. Eff ects on Sox6, Nrg1, Erbb4, Oct1 were confi rmed by real time RT PCR. Analyses of proteins and female hippocampus are in progress. Involvement of Nrg1, its receptor Erbb4 and Sox6 suggests eff ects on interneuron development. In postmitotic interneurons of PND6, Sox6 controlled interneuron subtype diversity. Expression changes were observed in interneuron-related genes. The
increase of Sox6 mRNA levels relative to mRNA levels of Sox5, its counterpart in postmitotic corticofugal projection neurons also suggests a specifi c eff ect in interneurons. Sox6 further controls gliogenesis in hippocampus; Sox6 overexpression represses specification and terminal diff erentiation of oligodendrocyte precursors. In conclusion, our investigation revealed convergent actions of diff erent types of behaviorally active chemicals on genes involved in the control of major developmental processes
in hippocampus.

Biography:

Dr Sandip Mukherjee received his PhD degree in the year 2007 from Jadavpur University, Kolkata, India and has published over 24 research articles and book chapter. He is an Assistant Professor (Senior Grade) at Department of Physiology, Serampore College since 2008. He has been serving as reviewers in different international journals with repute.

Abstract:

Cigarette smoking in regular habits affects our bodies in various ways and nicotine is the more abundant and most significant components of cigarette smoke. Epidemiological evidence strongly suggests an association between cigarette smoking and pancreatic injury. However, effects of cigarette smoking on pancreatic islets are still controversial. Impact and underlying mechanism of actions of folic acid and vitamin B12 on nicotine induced damage in pancreatic islets of rats are examined in the present study.  Male Wister rats were exposed to nicotine with or without supplementation of folic acid and vitamin B12. Folic acid and vitamin B12 in combination blunted the nicotine induced impairment in glucose tolerance, and levels of HbA1c and insulin in rats. Proinflammatory cytokines like TNF-α and IL-6, generation of reactive oxygen species, nitric oxide production and other oxidative stress parameters were also attenuated by folic acid and vitamin B12 in nicotine treated rats. Both, folic acid and vitamin B12 in combination also limits the nicotine induced changes in cell cycle and excessive apoptosis of the pancreatic β-cell along with altered Bcl-2, Bax, caspase-3 and caspase-9 expression and up regulation of iNOS and TNF-α. Nicotine-induced alteration in loss of mitochondrial membrane potential (Δψm) and release of cytochrome c also reversed by folic acid and vitamin B12 supplementation. In conclusion, folic acid and vitamin B12 protects against islet cellular oxidative stress, which is a critical step in nicotine-mediated islet injury, and improves islet cell functional status by scavenging free radicals, inhibiting the generation of pro-inflammatory mediators and apoptosis.

Biography:

PhD 1990 (Joint Scheme between Leeds Univ., UK, and Alexandria Univ., Egypt). Postdoctoral training at East Carolina Univ., USA. Chair, Pharmacology and Toxicology, Pharmacy, Alexandria Univ., Egypt. Chair, National Scientific Committee on Pharmacology Faculty Promotion. Publications: 107 papers in top international journals and 90 abstracts in international conferences. Research expertise: cardiovascular/renal neurobiology of drugs of abuse (ethanol, nicotine) and immunosuppressants.  Editorial boards positions in 9 international journals. Awards: Khalifa Award for Education in the Field of Scientific Research (United Arab Emirates), State Prize for Scientific Encouragement (twice), State Prize for Scientific Excellence, ACDIMA award (Jordon), Alexandria University Honorary Award.

Abstract:

The combined use of cyclosporine (CSA) and nonsteroidal antiinflammatory drugs (NSAIDs) in arthritic conditions is common in clinical practice. Because CSA or NSAIDs negatively impacts cardiovascular/renal functions when used individually, we asked if these two drug modalities would provoke more detrimental consequences when used together. The roles of endothelin receptor, inflammatory, and fibrotic pathways in these interactions have also been investigated. The treatment of rats with celecoxib, but not indomethacin, blunted the CSA-evoked increases in blood pressure (BP), renal perivascular fibrosis, and arteriolar endothelin receptor expression (increases in ETA and decreases in ETB receptors). Alternatively, exaggerated nephrotoxicity was seen upon simultaneous treatment with CSA plus indomethacin as evidenced by the (i) greater elevations in serum creatinine and renal oxidative stress, (ii) renal infiltration of inflammatory cells and worsening of fibrotic and necrotic profiles, and (iii) increased renal ET-1 and COX-2 expression. Unlike indomethacin, renal structural, oxidative, and molecular abnormalities caused by CSA were largely eliminated in rats treated concurrently with celecoxib. ETA receptor blockade by atrasentan ameliorated the hypertension and concomitant renal abnormalities caused by CSA/indomethacin regimen. On the other hand, ETB receptor blockade (BQ788) caused celecoxib-sensitive hypertension and renal dysfunction and potentiated the hypertensive effect of CSA. These findings suggest that COX-1/COX-2 selectivity of NSAIDs is pivotal for identifying their cardiovascular and renal impacts on CSA toxicity. Celecoxib, but not indomethacin, is more advantageous as an add-on therapy to CSA for arthritis management. The reliability of the current experimental findings needs to be corroborated with appropriate clinical investigations.

  • Workshop on Toxicology of Mixtures
Location: Olimpica-2

Session Introduction

Vesna Matovic

University of Belgrade, Serbia

Title: Co-treatment with PCBs potenciates Cd nephrotoxicity

Time : 14:45-15:15

Biography:

Vesna Matovic has completed her PhD at Faculty of Pharmacy, University of Belgrade, Serbia. She is Head of Department of Toxicology “Akademik Danilo
Soldatovic” and President of Serbian Society of Toxicology. She has published more than 250 papers in reputed journals and has been serving as an Editorial
Board Member and reviewer.

Abstract:

The nephrotoxic eff ect of cadmium (Cd) and polychlorinated biphenyls (PCBs), as widely spread toxic environmental pollutants that enter food chain and pose risk to human health, was investigated and compared with Cd—agent of wellknown nephrotoxicity. Six groups of rats were receiving 0.3, 0.6, 1.25, 2.5, 5 or 10 mg Cd/kg b.w./day as aqueous solutions of CdCl2, while nine groups were treated with diff erent dose combinations of Cd and PCBs, as Aroclor 1254 dissolved in corn oil, (1.25, 2.5 or 5 mg Cd/kg b.w./day with 2,4 or 8 mg PCBs/kg b.w./day). Two groups receiving only water or corn oil served as controls. Treatment of all animals was performed by oral gavage and lasted for 28 days. Cadmium levels were determined in blood and kidneys. Urea and creatinine in serum and relative kidney weight were determined. Blood and kidney Cd levels in groups treated with Cd only as well as in co-treated groups were signifi cantly higher if compared with controls, although PCBs did not exert significant eff ect on Cd content. Urea levels were signifi cantly higher in rats treated with all combinations of Cd and PCBs if compared with groups treated with Cd only, while only highest dose of Cd combined with diff erent doses of PCBs resulted in higher creatinine levels and relative kidney weight. Synergistic interactions between Cd and PCBs have been proven for urea levels indicating more profound nephrotoxic potency of this mixture when compared to Cd induced eff ect on kidneys.

Aleksandra Buha

University of Belgrade, Serbia

Title: Hepatotoxicity of Cd and PCBs mixture
Biography:

Aleksandra Buha has completed her PhD in Toxicology at Faculty of Pharmacy, University of Belgrade, Serbia. She is employed at the Department of Toxicology “Akademik Danilo Soldatović” and has published 13 papers in reputed international  journals

Abstract:

Hepatotoxicity is the well-documented adverse health effect of widelly spread environmental pollutants-cadmium (Cd) and polychlorinated biphenyls (PCBs), although hapatotoxic effects of their mixture still need to be evaluated. The hepatotoxic effects of Cd and PCBs mixtures were investigated in nine groups of rats treated orally during 28 days with different dose combinations of Cd as aqueous solutions of CdCland PCBs as Aroclor 1254 dissolved in corn oil (1.25, 2.5 or 5 mg Cd/kg b.w./day and 2, 4 or 8 mg PCBs/kg b.w./day), while groups treated with appropriate doses of single chemicals served as controls. At the end of experiment following parameters were estimated: relative liver weight, Cd and PCBs levels in liver and albumine content and activity of hepatic enzyme aspartate aminotransferase (AST) in serum. Relative liver weight was significantly higher in all groups treated treated with both Cd and PCBs. Furthermore, levels of both chemicals in liver were statistically higher than levels in groups treated with single chemicals indicating possible toxicokinetic interactions between these chemicals. Albumine content was significantly higher in all investigated co-exposed groups when compared to groups treated with PCBs only while the significance was obtained only for the highest doses of both chemicals when compared to Cd treated group. The activity of AST was significantly higher in all mixture treated groups when compared to controls. No toxicodinamic interactions between Cd and PCBs were observed for albumine and AST. Our study provides some insight into hepatotoxicity of Cd and PCBs mixtures and gives evidence that co-exposure to these chemicals can result in more profound hepatotoxicity than single chemicals can.

  • Genetic Toxicology| Toxicology Testing| Forensic Toxicology
Location: Olimpica-2
Speaker

Chair

Stefano Bonassi

IRCCS San Raffaele Pisana, Italy

Speaker

Co-Chair

Wei Zheng

Purdue University, USA

Session Introduction

Nan Mei

National Center for Toxicological Research, USA

Title: Mechanistic study of TEMPO-associated oxidative stress and genotoxicity

Time : 15:15-15:35

Biography:

Nan Mei after graduating from Hebei Medical University, China in 1984, started his scientific career in clinical cancer research and diagnosis as a Physician in a
university hospital. In 1997, he received his PhD degree from the University of Occupational and Environmental Health, Japan. He then extended his training on
assessing DNA damage as a Post-doctoral Fellow at the Cross Cancer Institute, Canada. In 2002, he joined the US FDA/NCTR. Currently his research focuses on
genetic toxicology and toxicogenomics. He has published more than 80 peer-reviewed research articles in prestigious journals and 11 book chapters.

Abstract:

The biological consequences of exposure to piperidine nitroxides is a concern, given their widespread use in manufacturing processes and their potential use in clinical applications. Previously, we have demonstrated that TEMPO (2,2,6,6-tetramethylpiperidine- 1-oxyl), a low molecular weight free radical, can induce cytotoxicity and genotoxicity in mammalian cells. Extending this earlier work, the present study investigates the underlying mechanisms of TEMPO-associated oxidative stress and genotoxicity, particularly the roles of reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) signaling. Our results demonstrate that TEMPO induced time- and concentration-dependent intracellular ROS production and glutathione depletion in mouse lymphoma L5178Y cells. TEMPO also induced apoptosis as demonstrated by increased caspase-3/7 activity, an increased proportion of annexin V stained cells, and decreased expression of anti-apoptotic proteins including Bcl-2, Bcl-xL and Mcl-1. N-acetylcysteine, a ROS scavenger, attenuated the ROS production and apoptosis induced by TEMPO. Moreover, Western blot analyses revealed that TEMPO activated γ-H2A.X, a hallmark of DNA damage, and c-Jun N-terminal kinases (JNK); a key member in the mitogenactivated protein kinase (MAPK) signaling pathway. Addition of SP600125, a JNK-specifi c inhibitor, blocked TEMPO-mediated JNK phosphorylation and also attenuated TEMPO-induced apoptosis. Th ese fi ndings indicate that TEMPO-induced apoptosis and toxicity are, at least in part, mediated by oxidative stress and activation of JNK in the MAPK pathway.

Eric Ezan

Health Technology Program-CEA, France

Title: Pharmacokinetic studies of protein drugs and assessment of their metabolism

Time : 15:35-15:55

Biography:

Eric Ezan studied Biological Engineering at the University of Compiegne, France. After a fi rst experience at the University of Waterloo (Ontario), he obtained a PhD degree at the University Paris V in Pharmacological Sciences (1989). He then joined the Institute Pasteur of Paris for two-year Post-doctoral experience. He was recruited by the CEA (Alternative Energies and Atomic Energy Commission) in 1991, where he became the Head of the Laboratory for Drug Metabolism at the CEA in 2000. This laboratory located at Saclay, south of Paris, is involved in the development of immunological methods and mass spectrometry for the discovery of biomarkers and quantifi cation of small molecular weight drugs and biologicals for preclinical and clinical applications. The laboratory also became a leader in the use of mass spectrometry approaches for the detection biological weapons. In 2014, he joined the CEA Program for the development of health technology.

Abstract:

Among the growing number of therapeutic proteins on the market, there is an emergence of bio-therapeutics designed from our comprehension of the physiological mechanisms responsible for their peripheral and tissue pharmacokinetics. Most of them have been optimized to increase their half-life through glycosylation engineering, polyethylene glycol conjugation or Fc fusion. However, our understanding of biological drug behaviors is still in its infancy compared to the huge amount of data regarding small molecular weight drugs accumulated over half a century. Unfortunately, therapeutic proteins share few resemblances with these drugs. For instance drug-targeted-mediated disposition, binding to glycoreceptors, lysosomal recycling, large hydrodynamic volume and electrostatic charge are typical critical characteristics that cannot be derived from our anterior knowledge of classical drugs. However, the numerous discoveries made in the last two decades have driven and will continue to drive new options in biochemical engineering and support the design of complex delivery systems. Most of these new developments will be supported by novel analytical methods for assessing in vitro or in vivo metabolism parameters.

Break: Networking and Refreshment Break 15:55-16:10 @ Foyer
Biography:

Qing Xia has completed her PhD from the Second Military Medical University and Post-doctoral studies from Duke University School of Medicine. She is the Vice Director of National Center of Biomedical Analysis, Beijing, China. She has published more than 20 papers in reputed journals and has been serving as a Member of the Chinese Committee of Bio-Safety on Transgenic Products.

Abstract:

A 52-week feeding study in Cynomolgus macaques was carried out to evaluate the safety of Bt-rice Huahui 1 (HH1), a transgenic rice line expressing Cry1Ab/1Ac protein. Monkeys were fed a diet with 20% or 60% HH1 rice, 20% or 60% parental rice (Minghui 63, MH63), normal diet, normal diet spiked with purifi ed recombinant Cry1Ab/1Ac fusion protein or bovine serum albumin (BSA) respectively. During the feeding trail, clinical observations were conducted daily, and multiple parameters, including body weight, body temperature, electrocardiogram, hematology, blood biochemistry, serum metabolome and gut microbiome were examined at regular intervals. Upon sacrifice, the organs were weighted, and the macroscopic, microscopic and electron microscopic examinations were performed. Th e results show no adverse or toxic eff ects of Bt-rice HH1 or Cry1Ab/1Ac fusion protein on monkeys. Th erefore, the present 52-week primate feeding study suggests that the transgenic rice containing Cry1Ab/1Ac is equivalent to its parental rice line MH63.

Biography:

Fabio Caradonna has completed his PhD and Postdoc on Cellular Biology at University of Palermo. He is Specialist in Clinic Pathology and in Bioethics. He is a group leader of “Genetics and Cell Biology” lab of STEBICEF Department (University of Palermo). He is an offi cial Reviewer of country and national projects and Editor in Chief of Journal of Carcinogenesis & Mutagenesis. He has an excellent experience in “Cytogenetics, Genotoxicity, DNA/chromosome methylation assessment”. He is an Assistant Professor of Human Genetics and Cytogenetics, Supervisor for PhD thesis and has published 31 ISI papers, 13 book chapters and 58 meeting abstracts..

Abstract:

Treating V79-Cl3 cells with 10 μM sodium arsenite (SA) for 24 h, we observed severe alterations in spindle morphology and aneuploidy; treating rat astrocytes with SA, we detected HSP70 induction and DNA damage. We assumed that SA
induced in dividing cells early genetic instability. Subsequently, we stabilized those V79-Cl3 cells in vitro dividing at the end of SA-treatment and maintained for long without SA (ASO cells). In ASO cells, we observed chromosomal rearrangements, increased spontaneous mutations, genome-wide DNA hypomethylation (GWDH), similarly to exposed cells. We inferred that a short-term SA exposure has long-term eff ects and that GWDH enhances the genetic instability. Consequently, we evaluated GWDH in HaCaT keratinocytes at several time points during expanded growth following SA removal. We found a persistent GWDH and some specifi c gene promoters (DNMT3A, DNMT3B, HMLH1) methylation changes. We suggest that the SA-treated cells undergo epigenetic reprogramming at gene/genome level that is durable over many cell generations in the absence of SA, contributing to long-lasting genomic instability SA-induced. Obtaining several individual clones isolated at different time points from the growing ASO cells, we observed in someone, chromosomal and morphological instability, higher ROS and berrant DNA methylation. We also noted that all the ASO clones with low SOD1 and high ROS acquired a transformed phenotype and moreover, increase of ROS was accompanied by defective telomerase activity. We propose that cells escaping the SA-induced death, perpetuate the memory of past exposure via ROS because of antioxidant and telomerase activity impairment and ultimately they acquire a transformed phenotype.

Rojas E

Universidad Nacional Autonoma de Mexico, Mexico

Title: mRNA and miRNA expression patterns associated to pathways linked to metal mixture health effects

Time : 16:50-17:10

Biography:

Rojas E has completed his PhD from UNAM, Mexico. He is a Full Professor in Biomedical Research Institute. He has published more than 75 papers in reputed
journals that has been cited more than 4500 times, and had been serving as an Editorial Board Member of Mutation Research Reviews and Mutation Research
Genetic Toxicology and Environmental Mutagenesis.

Abstract:

Metals are a major category of globally distributed pollutants that tend to accumulate in select tissues. Metal mixtures are a potential threat to human health by increasing disease risk. Recently, experimental data have linked altered miRNA expression with exposure to several metals, including As, Cd and Pb. Although, several human populations are exposed to low concentrations of As-Cd-Pb mixture, there are few data at respect to miRNA expression patterns. Thus, this study aims to evaluate global miRNA and mRNA expression changes induced by a metal mixture (NaAsO2, CdCl2 and Pb(C2H3O2)2•3H2O) to explore the role of miRNA-222 as a post-transcriptional regulator of RAD51C, a gene involved in homologous recombination of double-strand break DNA repair. Our results show that miRNA expression profi le responsible for the mRNA expression changes induced by metal mixture exposure are involved in cellular processes, including DNA repair, cell death, growth and proliferation related to the metal-associated pathologies (cardiovascular diseases and cancer). On the other hand, we found that miR-222 directly negatively regulates RAD51C expression and impairs homologous recombination of double-strand break DNA repair, generating genetic instability that could be related with cell transformation.

Biography:

Carmen Lucia Bassi Branco has completed her PhD at São Paulo University in 2004 and Post-doctoral studies at the same university in 2007. She is Professor at the Federal University of Mato Grosso since 2009, where she develops research in the mutagenesis area.

Abstract:

Lumefantrine (LF) is used in artemisinin-based combination therapies against malaria worldwide. It is genotoxic and mutagenic to human lymphocytes in vitro and may interact non-covalently with DNA minor groove surface. Considering that DNA binders are oft en topoisomerase inhibitors; in this study, we investigated the potential non-covalent interaction of LF with human topoisomerase II beta (hTOP2β) complexed to DNA by molecular docking study. Computer-assisted molecular analyses have been performed for predicting the possible interactions between hTOP2β-DNA complex and LF. The hTOP2β-DNA complex bound to LF was then assessed for interactions, energetic contributions, and for identifi cation of the best correlation between the LF conformations and their associated scores. The fused-tricyclic 9H-fl uorene rings in the LF chemical structure promote the intercalative binding into cleaved DNA sites present in hTOP2β-DNA complex. Since this is a polycyclic aromatic moiety, it gives the LF molecule the necessary planarity and aromaticity for intercalative binding to DNA base pairs in the cleavage sites, which showed aromatic interactions of -8.6 kcal/mol in the binding computational analysis for predicted binding affi nity energy. Th e N-dibutyl moiety and hydroxyl group from LF accommodate into the major groove and
hydrogen bond to nitrogen and oxygen atoms on the base-pair in the DNA segment. The N-dibutyl moiety also interacts with residues on the major groove side. Th e (4-chlorophenyl) methylidene moiety protrudes into the DNA minor groove side facing nearby residues from this protein–DNA interface. Th e hypothesis on the interaction of LF with topoisomerase II needs to be investigated using other approaches.

Biography:

Randa H. E. Osman has completed her PhD at the age of 43 years from University of Khartoum He is the head  of Bio-Pesticides and-Biofertilizers Department  and Director of the Rhizobium inoculants production unit at the Environment and Natural Resource and Desertification Research Institute (ENDRI), National Center for. She has published 4 papers in reputed journals and has been serving as a reviewer for some international journals. A senior scientist in the Tunisian Society for Microbial Ecology, (ATEM). A senior Member of Asia-Pacific Chemical, Biological & Environmental Engineering Society (APCBEES).

Abstract:

Two laboratory experiments were conducted to investigate the effect of different concentrations of Benomyl fungicide on the numbers of the main groups of soil micro flora and to elucidate percent fungicide degradation in sandy loam and clay loam soils in Sudan. Benomyl was applied in four concentrations; 0.032, 0.8, 3.2 and 8.0 mg/g soil. Counts of microorganisms in Benomyl treated soils were determined at 7, 15, 30 and 240 days’ intervals. Benomyl residue was determined at the same intervals using RP C18- HPLC. Results revealed the suppression of fungal flora in both soil types immediately after the first week of incubation. Numbers of organic nitrogen using bacteria increased earlier (15 days) in sandy loam soil compared to clay loam soil (30 days). While inorganic nitrogen using bacteria increased in numbers by Benomyl application at 15 days’ interval and then decreased in numbers up to the end of incubation period especially at the highest concentrations in both soil types. Benomyl completely suppressed actinomycetes in clay loam soil and was found to cause fluctuating effects on their numbers in sandy loam soil. Degradation of  Benomyl at the first three concentrations started earlier in sandy loam soil compared to clay loam  but the highest degradation values were recorded in clay loam soil after 240 days of incubation. At the highest concentration tested Benomyl underwent higher and faster degradation in clay loam soil compared to sandy loam.

Biography:

Omid Sabzevari has completed his PhD at the age of 29 years from Surrey University, and fellowship at Toronto University Faculty of Pharmacy. He is President of Iranian Society of Toxicology (IranTox) and President of Iranian Association of Pharmaceutical Scientists (IranAPS). He is Head of Basic and Clinical Toxicology Research Centre, TUMS. He is a scientist in fields of Mechanistic Toxicology & Pharmacology and Food Safety and has published more than 50 papers in reputed journals and has been serving as an editorial board member of repute. He was listed among Top 1% Scientists of the World according to ESI/ISI in May 2012.

Abstract:

Sepsis is a debilitating systemic disease and described as a severe and irregular systemic inflammatory reaction syndrome (SIRS) against infection. We employed CLP (Cecal Ligation and Puncture) model in rats to investigate anti-inflammatory and antioxidant effects of phloretin, as a natural antioxidant agent, and its protective effect on liver tissue damage caused by sepsis.Methods: Male Wistar albino rats were randomly divided into three groups: sham group, CLP induced sepsis group and phloretin treated CLP group. Sepsis was induced by CLP method. 50 mmol/kg Phloretin was administered intraperitoneally in two equal doses immediately after surgery.

Results: It was observed that blood urea nitrogen (BUN) and tumor necrosis factor alpha (TNF-α) levels were dramatically increased in the CLP induced sepsis group (43.88 ± 1.905 mg/dl, 37.63±1.92, respectively) when compared to the sham group.Moreover, tissue Glutathione (GSH) and liver nuclear factor ĸB (NF-ĸB p65) transcription factor values were higher in CLP induced sepsis group. This elevation was considerably reduced in the phloretin treated CLP group. No significant differences were observed in serum creatinine and creatinine phosphokinase levels.
Conclusions: The present study suggested that phloretin, as a natural protective agent, act against tissue damages introduced following the experimental sepsis induced model, likely caused by free oxygen radicals.

Biography:

Layla Borham professor of Clinical Pharmacology at Cairo and Umm AlQura Universities since 2004. She received, MSc and MD degrees from Cairo University Medical School. She has been working in Faculty of Medicine, Umm AlQura University, KSA for 15 years. During this period, she carried out a lot of scientific and social serving activities through her publications, scientific committee memberships, lectures and administrative work. In addition, she works in the Ministry of Health hospitals and primary health care centres giving awareness lectures to health care providers and patients.  She has been awarded a golden prize from Umm AlQura University for her overall services at the University.

Abstract:

Background: Increased con­cerns rose towards the side effects of chronic use of proton pump inhibitors (PPIs). The relationship between prolonged use of PPIs and bone metabolism, is still not totally established.
Objectives: Examine the association between the use of (PPIs) and the risk of development osteoporosis.
Methodology: 180 adult male rats were assigned to three groups (60 rats each). Group I served as control; whereas, group II (a, b), (i.p) omeprazole 20 mg/kg/day was administered for 4 and 8 weeks respectively; group III (a, b), (i.p) omeprazole 40 mg/kg/day was given for the same period. At the end of drug treatment, twenty rats from each subgroup were examined for bone mineral density (BMD), bone mineral content (BMC), serum calcium, phosphorus, parathormone, tartrate resistant acid phosphatase type 5b (TRACP5b), insulin-like growth factor 1(1GF-1) and Osteoprotegerin (OPG). The remaining 10 rats from each subgroup were left without treatment for the next 4 weeks to detect the reversal effects of the drug.
Results: BMD and BMC decreased in a dose and time dependent manners, with recovery. Serum calcium and phosphate decreased at the dose 40mg/kg for 8 weeks, with recovery of calcium after discontinuation of therapy but not phosphate. Parathormone increased compared to control with no recovery. TRACP5b increased at 20, 40 mg at 8 weeks with no recovery. IGF-1decreased in dose and time dependent manner, recovery only for 20 mg for 4 weeks. OPG shows no change.
Conclusion: The chronic use of high doses of omeprazole could adversely affect bone homeostasis.

  • Day 2 Breakout Session
Location: Olimpica-3
  • Plenary Session
Location: Olimpica-3
Biography:

Fawzy Elbarbry has completed his PhD and Post-doctoral studies from University of Saskatchewan College of Pharmacy (Canada). He joined Pacific University School of Pharmacy in 2008 as an Assistant Professor and in 2012, he was promoted to Associate Professor. He is also a Clinical Pharmacist at a major healthsystem in Oregon. He has published more than 30 papers and book chapters in reputed journals and more than 50 meeting proceedings and abstracts. He has been serving as an Editorial Board Member and frequent Reviewer for several publishers and granting agencies.

Abstract:

Aim: We have previously demonstrated that exposure of spontaneously hypertensive rats (SHR) to sulforaphane (SF) results in resisting the normal progressive rise in blood. Th is study aims to investigate the potential eff ect of these dietary doses of SF on hepatic drug metabolizing enzymes in SHR.
Methods: Rats were treated for eight weeks with SF (20 or 40 mg/kg) added to drinking water. At the end of treatment rats were euthanized, followed by preparation of liver microsomes and cytosols. Th e activity and/or protein expression of selected cytochrome P450 (CYP) enzymes and microsomal epoxide hydrolase (mEH) were measured in hepatic microsomes. Cytosolic fraction was utilized to measure total glutathione (GSH) level and activity of selected antioxidant enzymes.
Results: At the high dose, SF treatment resulted in a signifi cant reduction of CYP1A2 and CYP2C9 activities that were accompanied by a parallel decline in their apoproteins. Similarly, activities of CYP2B1/2 and mEH were inhibited only by high dose SF treatment. No eff ect of SF was observed on the rest of the studied phase I enzymes. On the other hand, both low and high doses of SF resulted in a signifi cant induction of both hepatic glutathione level and activities of superoxide dismutase (SOD) and catalase. Only the high dose SF induced the activities of hepatic glutathione-S-transferases (GST), glutathione reductase (GR) and glutathione peroxidase (GPx) to a signifi cant eff ect.
Conclusion: Th is study demonstrates that dietary doses SF has the potential to offer chemoprevention through stimulation of the endogenous antioxidants and inhibiting CYP enzymes involved in bioactivation of procarcinogens.

Biography:

Govindasamy Mugesh received his PhD in 1998 from the Indian Institute of Technology, Bombay. He is an author of more than 120 publications in international peer reviewed journals. He received several awards and recognitions. His research interests include the chemistry of thyroid hormone metabolism and development of novel therapeutics for endothelial dysfunction and neurodegenerative diseases. He serves in the editorial boards of Organic & Biomolecular Chemistry, ACS Omega, Bioorganic Chemistry and Scientifi c Reports.

Abstract:

Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and the biological system's ability to detoxify these reactive intermediates. It is well known that oxidative stress is responsible for several disease states. Both Type I and II diabetics display increased levels of ROS such as free radicals and the onset of diabetes is closely associated with oxidative stress. It has also been associated with diverse diseases, including cancer, renal disease, and neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Although plants and animals maintain the level of antioxidants, such as glutathione (GSH), vitamins C, A and E as well as enzymes such as catalase, superoxide dismutase and various peroxidases, insufficient levels of antioxidants, or inhibition of the antioxidant enzymes, cause oxidative stress. Our group focuses on the development of enzyme mimetic redox modulators that can be used as drugs for diseases associated with enhanced level of ROS and that can combat oxidative stress without affecting the cellular antioxidant systems. In this lecture, various selenium compounds and their effect on ROS in mammalian cells will be discussed.

Mohanan PV

Sree Chitra Tirunal Institute for Medical Sciences and Technology, India

Title: Toxicology of polymeric biomaterials: A regulatory approach
Biography:

Mohanan P V is working as a Scientist & Head, Toxicology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST). He has Postdoctoral experience from the University of Tsukuba, Japan and Doctoral degree from the University of Kerala. As a toxicologist at SCTIMST with more than 28 years of experience, he has been intimately associated with all the medical devices/technologies developed at SCTIMST. As a Scientist, he has established his own area of research and pursued them with several externally funded projects as Principal Investigator. He has made significant contributions for the development of medical device industry and medical device regulations in India, and India getting GLP membership in OECD countries. He is the senior most GLP Inspector (DST, New Delhi) of the country and a Certified Biological Safety Specialist. He received several national and international awards and honors like, certificate of appreciation from the Hon. Minister of Science and Technology, Govt. of India for the contribution to India getting full adherent status on GLP from OECD, JSPS Fellowship, JSPS Bridge Fellowship, Country Correspondent for the World Library of Toxicology, Senior Toxicologist Fellowship from IUTOX, USA. He was the Secretary General of Society of Toxicology, India and presently he is the General Secretary of Indian JSPS Alumni Association. He is a Fellow of Society of Toxicology, Fellow of Society of Applied Biotechnology and Fellow of Academy of Sciences for animal welfare. He has authored 137 peer reviewed full papers, 4 book chapters, edited 3 books and 4 conference proceedings.

Abstract:

Polymeric biomaterials are widely used in clinical applications such as for drug delivery, tissue engineering, bio-medical sensing, skin grafting, medical adhesives etc. Polymeric biomaterials are chosen for different applications depending on their properties. They act as substitutes for soft and hard tissues in the body. The objective of the toxicological studies of polymeric materials, intended for the fabrication of medical devices, is to investigate the potential biological hazards by careful observations for unexpected adverse reactions or events in humans during clinical use of the medical devices. The toxicity/biocompatibility evaluation of polymeric materials assesses the risk of adverse health effects due to normal use and likely misuse of a device. Adverse health effects could result from exposure to the materials from which a device is made; preclinical assessment of the toxic potential of such materials or components is needed to minimize the potential hazard to the patient. It was well aware that the medical device comprises several components made from different materials; the ideal procedure from a toxicological point of view would be, to evaluate extracts of the components separately. However, in some situations this is not practical, and extracts of the whole device may be used instead. The amount of leachable substances released to the extraction media is related to the surface area and thickness of the product to be extracted. The range of potential biological hazards is wide and may include; short term effects (like acute toxicity, irritation, sensitization, haemolysis and thromobogenicity) and long term effects (such as sub chronic and chronic toxicity, sensitization, genotoxicity, carcinogenicity and effects on reproduction including teratogenicity). Due to the diversity of medical devices, it is recognized that not all the tests identified in a category will be necessary or practical for any given device. It is indispensable for testing that each device shall be considered on its own merits. The details of the toxicity assays will be discussed during the presentation.

  • Pharmacological and Toxicological Methods | Systems Pharmacology | Toxicovigilance
Location: Olimpica-3
Speaker

Chair

Swamy KB

Mahsa University-Jalan Elmu Off Jalan University, Malaysia

Speaker

Co-Chair

Fawzy Elbarbry

Pacific University, USA

Session Introduction

J Sattayasai

Khon Kaen University, Thailand

Title: Dark purple glutinous rice Var. Luem Pua tea prevents DSS-induced colitis in mice

Time : 13:25-13:45

Biography:

J Sattayasai has completed her PhD from Monash University. She is now an Associate Professor of Pharmacology

Abstract:

Infl ammatory Bowel Disease (IBD) is characterized by chronic and relapsing inflammation of the gastrointestinal tract which is associated with increased risk of developing colitis-associated cancer. Although many chemical-induced colitis models were developed, dextran sulfate sodium (DSS)-induced colitis model was widely used to assess the therapeutic potential of treatments for IBD. In this study, the eff ects of aqueous extract of dark purple glutinous rice var. Luem Pua (LP) tea on DSS-induced colitis were evaluated. Aqueous extract of LP tea was prepared and dose used was expressed as dried weight of LP tea. Female ICR mice were forced fed with distilled water or LP extract 2 or 5 g/kg/day for seven consecutive days. On each day, 2 hours aft er feeding, water containing 2% DSS was supplied to all groups except the control group. DSS-induced colitis was scored with disease activity index (DAI) and the colon length, represented the severity of infl ammatory lesions in colon, and spleen weight, represented infl ammation stage, were evaluated. Th e results showed that LP extract antagonized the reduction of the colon length, the increase in DAI and the increase in spleen weight caused by DSS indicated the reduction of the inflammation by LP extract treatment. Recently, we have shown that LP contains quite high level of cyanidin-3-glucoside (C3G) with a high antioxidant activity. C3G is one of the active anthocyanin suggested to have benefi t in IBD. Our data suggest that drinking LP tea might have the beneficial effects in preventing and treating colitis and IBD.

Biography:

Poppenborg Sabine M has completed her PhD from University of Bielefeld, Germany, University of Montpellier, France and Post-doctoral studies from MRC Medical Research Council, Cambridge, UK. Since 2007, she is a Scientist in the Pharmacology/Toxicology unit of medac Gesellschaft für klinische Spezialpräparate mbH, Germany, a pharmaceutical company specialised on products for oncology, autoimmune diseases and urology.

Abstract:

A new pegylated recombinant E. coli L-asparaginase (PEG-rASNase MC0609) was designed by medac GmbH (Germany) to improve pharmacokinetic (PK) characteristics of pegylated L-asparaginase in comparison to pegaspargase (Oncaspar®) used as first-line treatment in patients with acute lymphoblastic leukaemia (ALL). Comparative PK, pharmacodynamic (PD) and immunogenicity studies were performed in Beagle dogs aft er single-dose intravenous (i.v.) administration of MC0609 or pegaspargase. Striking differences in PK and PD properties between both pegylated preparations were observed. Th e different PK characteristics were confi rmed by a population pharmacokinetic (PopPK) analysis. PK parameters of pegaspargase in Beagle dog were in the same range than the parameters determined in paediatric ALL patients. Therefore, the Beagle dog was considered a clinically relevant model for PK evaluation of pegaspargase. In addition, the potential impact of pre-existing anti- PEG antibodies on the ASNase activity of PEG-rASNase MC0609 and pegaspargase was investigated in immune competent B6D2F1 hybrid mice. Anti-PEG IgM antibodies were successfully induced in mice after repeated i.v. administration of 40 kDa PEG-Diol without being conjugated to a carrier. All animals detected “positive” for anti-PEG IgM antibodies and control animals (without prior PEG-Diol pre-sensitisation) were treated once i.v. with PEG-rASNase MC0609 or pegaspargase. ASNase activity profiles were obviously not infl uenced by the IgM positivity of animals. No accelerated decrease of ASNase activity was observed irrespective of successful PEG-Diol pre-sensitisation and presence of acquired anti-drug-IgG and/or anti-PEG IgM antibodies.

Biography:

Ajeya Nandi has gained her Post-graduate degree in Human Physiology from University of Calcutta, India in 2013. She is working as DST-INSPIRE Fellow in the Immunology Laboratory of University of Calcutta since 2013 and submitted her PhD thesis. She has published quite a good number of research articles. Her research has focused on the role of TLR-2 and CCR-2 in the host pathogen interaction during acute Staphylococcal infection.

Abstract:

Recruitment of monocytes from the bone marrow into the bloodstream and then to the sites of infection is regulated by CCL-2/CCR-2 signaling. But, involvement of CCL-2/CCR-2 signaling in the killing of S. aureus by murine fresh bone marrow cells is a pertinent question. The intermittent link of ROS and NF-κB/p38-MAPK mediated MCP-1 production in CCR-2 signaling has prompted to determine whether neutralization of CCR-2 augments the response of murine fresh bone marrow cells (FBMC) after S. aureus infection utilizing ROS production and cytokines in the killing of S. aureus. It was observed that FBMCs treated with anti-CCR-2 antibody released less ROS and NO on encountering S. aureus infection compared to CCR-2 non-neutralized FBMCs also correlating with reduced killing of S. aureus in CCR-2 neutralized FBMCs. Staphylococcal catalase and SOD also found to play a role in protecting S. aureus from the ROS mediated killing of FBMC. CCR-2 neutralized FBMCs infected with S. aureus exhibit less production of TNF-α, IFN-γ and IL-6 with increased IL-10 as compared to CCR-2 intact FBMCs. S. aureus infection to CCR-2 intact FBMCs pretreated with either NF-κB or p-38-MAPK blocker caused less MCP-1 suggesting that NF-κB or p-38-MAPK is required for MCP-1 production by FBMCs. Moreover, blocking of CCR-2 along with NF-κB or p-38-MAPK showed elevated MCP-1 production and reduced CCR-2 expression. Therefore, inhibition of CCR-2 exacerbates the murine fresh bone marrow cells response to S. aureus infection by utilizing the ROS production and by regulating the cytokine response.

Biography:

Vanda Maria Falcão Espada Lopes de Andrade graduated in Biology in 1992 and obtained a Master’s degree in Animal Biodiversity Conservation in 1998, both from Faculdade de Ciências da Universidade de Lisboa. She has completed her PhD in Pharmacy/Toxicology from Faculdade de Farmácia da Universidade de Lisboa, Portugal in 2014. She is Assistant Professor in Escola Superior Agrária de Santarém, Instituto Politécnico de Santarém since 2013, where she coordinates the curricular units of Toxicology since 2014; and since 2015, Pollution and Ecotoxicology. She has published 9 papers in international journals, performed 15
communications (4 oral presentations and 11 poster presentations) and 8 seminars.

Abstract:

Arsenic (As), manganese (Mn) and lead (Pb) are neurotoxic metals/metalloids that occur as mixtures in specific settings, like mines. Eff orts have been made to identify biochemical biomarkers (BMs) of neurotoxicity which can aid an early detection, progression or outcome of treatments. Th e complexity of the nervous system, individual variability and ubiquity of neurotoxic mixtures, is leading to the belief that multiparameter analysis through the integration of various markers may establish robust correlations between BMs and individual’s health status. Metals, including As, Mn and Pb, induce specific and different changes in heme metabolites excretion patterns, and its accumulation can cause neurotoxicity. The aim of this work was to generate 2 predictive models: (A) simpler and designed to detect neurotoxicity and (B) to predict the magnitude of these effects, individually. A group of Wistar rats were co-exposed for 8 days to Pb, As and Mn; a control group was used. Motor activity was evaluated and 24 h urine was collected. Urinary delta aminolevulinic acid (ALA U) and total porphyrins (Porf U) were determined by spectrophotometry and combined by multiple regressions to detect motor activity decrement (model A). Th e urinary porphyrin profile was determined by HPLC and used to predict the number of ambulation’s and rearing using the same statistical method (model B). All subjects were correctly classified regarding to motor activity decrease (model A) and average errors of 2 ambulation or rearing counts were obtained with model B. Th is work suggests that BMs integration methodologies are promising to assess “Real-Life” scenarios of exposure to chemical mixtures.

Yulia Pushkar

Purdue University, USA

Title: X-ray fluorescence imaging in toxicology

Time : 14:45-15:05

Biography:

Yulia Pushkar has completed her PhD in Biophysics at Freie Universität Berlin, Germany and Post-doctoral studies at University of California, Berkeley & Lawrence Berkeley National Lab. She is an Associate Professor of Physics and has published over 60 research articles including these in Science, Nature, Journal of American Chemical Society and PNAS.

Abstract:

Atomic transitions in elements, including Mn, Fe, Cu, Zn, Pb relevant in toxicology can be excited upon interaction with X-rays in 10-13 keV energy range. Recording resulting X-ray fluorescence (XRF) with high spatial resolution results in quantitative images of metal ion distributions in tissue sections. Different X-ray focusing optics allows for tissue level imaging (5-20 micron) resolution or subcellular level imaging (30-200 nm) of distributions of biologically relevant (Fe, Cu, Zn) and toxic (Mn, Pb). Development of beamlines with high X-ray photon flux at 3rd generation synchrotron sources allows to obtain high resolution XRF maps of ppm amounts of elements in thin tissue sections. Using XRF, we studied Mn distribution in rat model of occupational Mn exposure. We found that globus pallidus and substantia nigra compacta are areas in the brain that accumulate most Mn. Imaging the Mn distribution in dopaminergic neurons, we determined that intracellular Mn range between 40–200 micromolar; concentrations as low as 100 micromolar have been observed to cause cell death in cell cultures. This is a first direct link between Mn exposure and Parkinson's disease. We have previously reported localized Cu-rich aggregates in astrocytes of the subventricular zone in rodent brains with Cu concentrations in the hundreds of millimolar. Based on a [S]/[Cu] ratio and X-ray absorption spectroscopy, metallothionein is proposed as a binding protein. An analysis of metallothionein (1,2) knockout mice by XRF will be presented.

Biography:

Abstract:

Introduction & Objective: In the modern world, soy bean as a valuable meal is used for providing protein and some essential body needs. The stomach also as a part of alimentary canal has its own role in mechanical and chemical digestion. The objective of this study is evaluation of the effects of soy meal on histological and histometrical features of the stomach and also on biochemical factors of blood serum. 

Methods: In this experimental study, a total of thirty immature female mice of Balb/C were selected at three weeks of age. Then on the basis of three types of diets, the mice were divided into three groups as; the group A or control, fed on a diet of full protein, the group B fed on a diet of 40% soy meal and the group C fed on a diet of 20% soy meal. After three months, the mice were anesthetized, and blood samples were obtained from the heart for determining the serum level of some hematologic factors such as urea, total protein, cholesterol and LDL. Then the stomach was removed, some tissue sections were prepared and stained with H&E. After histological study, the stomach was subjected to histometric evaluation. The histometric data were surveyed by a light microscope equipped with Axiovision software and the thickness of mucosa, submucosa, musculature, also depth of the pits and the number of parietal cells were measured. For data analysis, One Way ANOVA was used to compare the control group with experimental groups and Tukey test was used to compare the groups with each other. The significance level was considered as P<0.05.                                                

Findings: Soya bean consumption didn,t cause  histological changes.In the more precisely histometric study, the results showed that in non glandular portion of the stomach, between the control group compared with the groups fed on soy meal, there was significant increase in thickness of mucosa in the experimental group B (676±99.45) compared with the control group (427±77.53) and also in thickness the muscular layers in the experimental group C )233.30±84.69) compared with the control group (104.05±11.71), (P<0.05). In the glandular portion also significant increase in thickness of mucosa in the experimental group B (1041.36±167.02) and C (1331.73±143.32) compared with the control group (615.29±83.14), in depth of pits in the experimental group B 134.53±14.60) and C (154.29±20.25) compared with the control group (94.79±12.93), in parietal cells in the experimental group B (15.66±4.45) and C (30.50±13.61) compared with the control group (9.83±1.47) and muscular layers in the experimental group B 211.59±53.68) and C (195.72±67.89) compared with the control group (155.73±28.23) was observed (P<0.05). However a significant decrease in serum level of cholesterol in the experimental group B (87.76±20.53) and C (83.03±16.06) compared with the control (117.70±20.71), serum level of urea in the experimental group B (36.23±10.43) and C (40.58±12.14) compared with the control group (65.33±7.28) and also LDL value in the experimental group B (5581.6±470.90) and C (5689.1±479.79) compared with the control group (6907.1±37.64) was observed (P<0.05).

Conclusion: It seems that long term consumption of soy bean could affect on the stomach mucosa and proliferation of parietal cells and also could decrease the serum levels of cholesterol, urea and LDL.

  • Pharmacology | Current Advances
Location: Olimpica-3
Speaker

Chair

Lisa Vaccari

Elettra Sincrotrone Trieste, Italy

Speaker

Co-Chair

Alan Poole

European Centre for Ecotoxicology & Toxicology of Chemicals, Belgium

Session Introduction

Giulio Sancini

University of Milano, Italy

Title: From the lungs to the brain: The fantastic voyage of nanoparticles targeting beta-amyloid (Aβ)

Time : 15:25-15:45

Biography:

Giulio Sancini is Assistant Professor of Physiology; Specialist in Applied Pharmacology, he has focused his research activity mainly on neurosciences, nanomedicine and nanotoxicology. His research has been funded by European FP7 (NAD Project, nanoparticles for diagnosis and therapy of Alzheimer’s disease, winner of The Best Project award in the field of Industrial Technologies) and FP6 (BONSAI project). He has published more than 45 papers in reputed journals and has been serving as an Editorial Board Member of repute. He is Head of the Physiology Unit at the Dept. of Medicine and Surgery of the University of Milano-Bicocca.

Abstract:

The brain is always confronted with the dilemma of the protection from noxious substances from the blood and the delivery of vital metabolites. Endothelial cells, forming together with other cells the blood-brain barrier (BBB), are known as the “Gatekeepers” of this trafficking. On the one hand, the protection from toxic molecules is achieved by the obstruction of the paracellular pathway with tight junctions that fuse brain capillary endothelia into a continuous tubular cell layer. On the other hand, vital molecules are transported from the blood by means of active trans-cellular mechanisms. Recent applications in nanomedicine focuses on nanoparticles (NP) as they are promising tools for site-specific delivery of drugs and diagnostic agents, through the possibility to functionalize their surface with target-specific ligands. Treatment options for Alzheimer’s disease (AD) are limited because of the inability of drugs to cross the BBB. Previously, we showed that intraperitoneal administration of liposomes functionalized with phosphatidic acid and an ApoE-derived peptide (mApoE-PA-LIP) reduces brain beta-amyloid (Aβ) burden and ameliorates impaired memory in AD mice. Among the different administration routes, pulmonary delivery is a field of increasing interest not only for the local treatment of airway diseases but also for the systemic administration. We investigated lung administration as an alternative, non-invasive NP delivery route for reaching the brain. Our results show that mApoE-PA-LIP were able to cross the pulmonary epithelium in vitro and reach the brain following in vivo intratracheal instillations. Lung administration of mApoE-PA-LIP to AD mice significantly decreased total brain Aβ (–60%; p<0.05) compared to untreated mice. These results suggest that pulmonary administration could be exploited for brain delivery of NP designed for AD therapy.

Biography:

Friday E Uboh completed his PhD from University of Calabar, Calabar, Nigeria, and is presently an Associate Professor of Biochemistry, with Toxicology as his area of research interest. He served as the acting Head of Biochemistry Department in the Department of Biochemistry University of Calabar, Calabar, Nigeria, from 2011 to 2013. He is a member of Nigerian Society of Biochemistry and Molecular Biology, and Institute of Public Analysts of Nigeria. He has more than 60 papers published in reputable journals, and is a reviewer and Editorial Board Member of many journals of repute. He has also presented many conference papers locally and internationally.

Abstract:

The plasma and liver tissue hydrocarbon contents, superoxide dismutase (SOD) and catalase (CAT) activities, malondialdehyde (MDA) and glutathione (GSH) levels of rats orally exposed to gasoline were assessed in this study. Eighteen adult male albino Wistar rats (210.0±20.0 g), distributed into three groups, of six rats each were used in the study. Rats in groups one and two, which served as controls, were given distilled water and sunflower oil respectively, while rats in group three (test group) were given 2 ml/kg b.wt. of gasoline in sunflower oil vehicle, for thirty, sixty and ninety days. At the end of the respective exposure periods, the animals were sacrificed, and relevant tissues collected and processed for analyses. The types and concentrations of hydrocarbons in the plasma and liver tissues were analysed by gas chromatography with flame ionized detector (GC-FID), while SOD and CAT activities, MDA and GSH levels were analysed by standard spectrophotometric methods. The results obtained from this study showed the presence of benzene, toluene, ethylene and xylene (BTEX) in the plasma and liver tissues of rats exposed to gasoline at concentrations significantly (p<0.05) higher than the respective concentration recorded for the controls; and that the plasma and liver tissue MDA level was significantly (p<0.05) higher, while SOD, CAT and GSH activities were significantly (p<0.05) lower in test rats, compared respectively to the control groups. However, the plasma and liver tissue BTEX, MDA, SOD, CAT and GSH activities recorded in rats exposed for sixty and ninety days were significantly (p<0.05) different from the activities  recorded in rats exposed for thirty days, while no significant (p>0.05) difference was recorded between sixty and ninety days of exposure. This suggests that BTEX are largely absorbed from the GIT, and distributed within the body tissues, including the blood and liver tissues, following sub-chronic oral exposure to gasoline. Hence, that the raised plasma and liver tissue MDA, and reduced SOD, CAT and GSH activities in test animals may be attributed to the raised tissue BTEX levels. The results of this study therefore give a strong indication that BTEX is likely implicated in gasoline induced oxidative stress in rats.

Biography:

Pietro Marini has completed his PhD in Pharmacology, Toxicology and Pharmacognosy from La Sapienza University of Rome and Post-doctoral studies from Italian National Reasearch Council. He has published papers and book chapters in reputed journals moslty related to the cannabinoid recepotors pharmacology.

Abstract:

Cannabinoids are well known analgesic agents and common drugs of abuse. Both acute and chronic use of these drugs is associated with the development of tolerance and dependence. So far, the mechanism(s) underlying the acute dependence induced by drugs of abuse remain poorly understood and their elucidation is crucial for the understanding of the mechanisms underlying the chronic dependence. Preliminary results, clearly demonstrate that pre-stimulation of the cholinergic system increases levels of intracellular calcium in response to acute stimulation of cannabinoid receptors, thus suggesting a crucial role of the cholinergic system in the regulation of CB1 receptors activity, through the mobilization of intracellular calcium. Moreover, there is ample evidence that increases of intracellular calcium activate a series of transcription factors involved in gene regulation. However, the role played by acetylcholine and by intracellular calcium in the regulation of these transcription factors in the context of the CB1 receptor stimulation is largely unexplored. The novel findings presented here demonstrate a new cross talk mechanism between M3 and CB1 receptors that potentially could lead to a new pharmacological approach (development of combination therapies) while maintaining the desired effect (analgesia) could limit the development of dependence induced by the cannabinoid receptor stimulation.

Biography:

Saviour U Ufot completed his BSc in Biochemistry and MSc in Pharmacology from University of Calabar and Ibadan respectively. He completed his PhD in Biochemistry (Biochemical and Environmental Toxicology) from University of Calabar in 2014. He was a Lecturer in the Department of Pharmacology, University of Ilorin, Nigeria from 1993 to 1998. He is presently working with Total Exploration and Production Nigeria Limited as a Health, Safety and Environment specialist. He has published over 14 papers in reputable journals and has attended many scientific seminars and conferences.

Abstract:

This study assessed the concentrations of blood benzene, toluene, ethylmethylene, xylene, and total polycyclic aromatic hydrocarbons (PAH), some oxidative stress markers (MDA, SOD and CAT) and haematological indices in male albino Wistar rats orally exposed to bonny light crude oil (BLCO). Eighteen rats, weighing 150–l80 g, and distributed into three groups of six rats each, were used in this study. Rats in groups one and two, which served as the control groups, were respectively administered distilled water and vegetable oil only; while rats in group three (test group) were orally administered 60 mg/kg bwt of BLCO daily for 30 days. At the end of the exposure period, the animals were sacrificed and the blood samples collected for the analysis of some haematological indices, blood oxidative stress markers and hydrocarbon concentrations. All the analyses were carried out using standard laboratory methods. The results showed that blood benzene, toluene, ethylmethylene, xylene, and total polycyclic aromatic hydrocarbons (PAH) recorded for rats exposed to BLCO (0.066±0.004, 0.641±0.032, 0.470±0.030, 0.112±0.009, and 12.540±0.720 ug/dl, respectively) were significantly (p<0.05) higher compared with the concentrations recorded for rats in group one (0.020±0.001, 0.015±0.001, 0.010±0.000, 0.031±0.001, and 2.270±0.120 µg/dl, respectively) and two (0.021±0.001, 0.016±0.001, 0.010±0.001, 0.031±0.001, and 2.271±0.011 µg/dl, respectively). It was also observed from the results of this study that exposure to BLCO produced a significant (p<0.05) oxidative stress condition (decreased blood CAT and SOD activities and increased MDA concentration), and haematotoxicity (decreased RBC, Hb, PCV, and increased WBC and some differential cells) in male rats, compared with the control rats. It may therefore be concluded that benzene, toluene, ethylmethylene, xylene, and polycyclic aromatic hydrocarbons (PAH) are likely implicated in crude oil induced oxidative stress and haematotoxicity recorded in this study for male rats.

Matteo Micucci

University of Bologna, Italy

Title: Nutraceuticals for hypertension care: A network based approach

Time : 17:00-17:20

Biography:

Matteo Micucci completed his graduation in Pharmacy at Bologna University. In 2010, he worked in the laboratory of Dr. RRJ Arroo, Leicester School of Pharmacy, De Montfort University, UK. He was a Guest Scientist in the Department of Chemistry of Natural Substances, University of Naples “Federico II”, Italy. He awarded European PhD in Pharmaceutical Sciences at Bologna University in 2012. He is a Scientific Consultant, in the field of Nutraceutical, Alternative and Complementary Medicines, at Segreteria Particolare of a Senator of the Italian Republic. He is a Research Fellow Scientist at Department of Pharmacy and Biotechnology, University of Bologna.

Abstract:

Several diseases with a high incidence including those pertaining cardiovascular system, are due to modifications of many molecular networks influencing each other’s. The network based approach is based on the strategy named “network target multi components” and “network target single chemical” strategies. In different traditional systems, including Traditional Chinese Medicine (TCM) and ayurveda, poly-herbal formulations are considered efficient approaches to the treatment of multifactorial diseases. Nutraceutical science is mainly aimed at identifying the chemical composition and the mechanisms of action of complex mixtures, including the vegetal extracts. In this study, we focused on primary hypertension, representing a multifactorial pathology strongly predisposing to cardiovascular events. Many vegetal extracts with antihypertensive activities modulate several targets determining multiple cardiovascular beneficial effects. Among others, extracts from Olea europaea L. leaves and Hibiscus sabdariffa L. flowers interfere with different pathways, producing a hypotensive activity. In this work, we evaluated the cardiovascular effects and the toxicological profile of a Nutraceutical Formulation (NF) based on a mixture of a Olea europaea L. leaves extract (OEE) and a Hibiscus sabdariffa L. flowers extract (HSE) in the ratio of 13:2 using in vitro biological assays. The NF exerted a vasorelaxant effect (IC50=2.38 mg/mL) and a negative chronotropic effect (IC50=1.04 mg/mL) at concentrations lower than those producing smooth muscle spontaneous contractility alterations in the other organs. These experimental data suggest a potential application of this food supplement for contributing and managing preclinical hypertension.

Biography:

Ayşegül Küçük has completed her PhD from Erciyes University and Post-doctoral studies from Erciyes University School of Medicine. She is a member in Department of Physiology at the Medical Faculty of Dumlupinar University. She has published more than 25 papers in reputed journals.

Abstract:

Change in blood supply is responsible for anesthesia related abnormal tissue and organ perfusion. Decreased erythrocyte deformability and increased aggregation may be detected after surgery performed under general anesthesia. It was shown that non-steroidal anti-inflammatory drugs decrease erythrocyte deformability. Lornoxicam and/or ibuprofen intravenous administration for postoperative pain management is becoming more common. In this study, we aimed to investigate effects of lornoxicam (2 mg/kg) and ibuprofen (30 mg/kg) on erythrocyte deformability, liver and renal blood flow in male rats. 18 male Wistar albino rats were randomly divided into three groups as lornoxicam group (group L), ibuprofen group (group İ) and control group (group C). İntravenous administrations were done in all groups except group C. Liver and renal blood flows were conducted by laser Doppler and the euthanasia via intra-abdominal blood uptake was performed. Erythrocyte deformability was measured using a constant flow filtrometry system. Lornoxicam and ibuprofen increased the relative resistance which shows the erythrocyte deformability of rats (p=0.016). Comparison of group L and group I revealed no statistically different results (p=0.694) where group L and group I revealed statistically higher results than group C (p=0.018, p=0.008). Liver and renal blood flows were significantly lower than that measured in group C. We believe that lornoxicam and ibuprofen may lead to functional disorders related to tissue perfusion as a result of both decreased blood flow and erythrocyte deformability. Further studies regarding these issues are thought to be essential.

Layla Ezzat Borham

Umm Al-Qura University, Saudi Arabia

Title: The effect of proton pump inhibitors on bone mineral density in rats

Time : 17:40-18:00

Biography:

Layla Ezzat Borham is a Professor of Clinical Pharmacology at Cairo and Umm Al-Qura Universities since 2004. She completed his MSc and MD at Cairo University Medical School. She has been working in Faculty of Medicine, Umm Al-Qura University, KSA for 15 years. During this period, she carried out a lot of scientific and social serving activities through her publications, scientific committee memberships, lectures and administrative work. In addition, she works in the Ministry of Health hospitals and primary health care centres giving awareness lectures to health care providers and patients. She has been awarded a Golden Prize from Umm AlQura University for her overall services at the University.

Abstract:

Background: Increased con­cerns rose towards the side effects of chronic use of proton pump inhibitors (PPIs). The relationship between prolonged use of PPIs and bone metabolism is still not totally established.
Aim: Aim of this study is to examine the association between the use of (PPIs) and the risk of development osteoporosis.
Method: 180 adult male rats were assigned to three groups (60 rats each). Group I served as control; whereas, group II (a, b), (i.p) omeprazole 20 mg/kg/day was administered for four and eight weeks respectively; group III (a, b), (i.p) omeprazole 40 mg/kg/day was given for the same period. At the end of drug treatment, 20 rats from each subgroup were examined for bone mineral density (BMD), bone mineral content (BMC), serum calcium, phosphorus, parathormone, tartrate resistant acid phosphatase type 5b (TRACP5b), insulin-like growth factor 1(1GF-1) and osteoprotegerin (OPG). The remaining 10 rats from each subgroup were left without treatment for the next four weeks to detect the reversal effects of the drug.
Results: BMD and BMC decreased in a dose and time dependent manners with recovery. Serum calcium and phosphate decreased at the dose 40 mg/kg for eight weeks with recovery of calcium after discontinuation of therapy but not phosphate. Parathormone increased compared to control with no recovery. TRACP5b increased at 20, 40 mg at eight weeks with no recovery. IGF1 decreased in dose and time dependent manner, recovery only for 20 mg for four weeks. OPG showed no change.Conclusion: The chronic use of high doses of omeprazole could adversely affect bone homeostasis.

Biography:

Omid Sabzevari has completed his PhD from Surrey University, and Fellowship at Toronto University Faculty of Pharmacy. He is President of Iranian Society of Toxicology (IranTox) and President of Iranian Association of Pharmaceutical Scientists (IranAPS). He is Head of Basic and Clinical Toxicology Research Centre, TUMS. He is a Scientist in the fields of Mechanistic Toxicology & Pharmacology and Food Safety and has published more than 50 papers in reputed journals, and has been serving as an Editorial Board Member of repute. He was listed among Top 1% Scientists of the World according to ESI/ISI in May 2012.

Abstract:

Introduction: Sepsis is a debilitating systemic disease and described as a severe and irregular systemic inflammatory reaction syndrome (SIRS) against infection. We employed CLP (Cecal Ligation and Puncture) model in rats to investigate anti-inflammatory and antioxidant effects of phloretin, as a natural antioxidant agent, and its protective effect on liver tissue damage caused by sepsis.
Methods: Male Wistar albino rats were randomly divided into 3 groups: Sham group, CLP induced sepsis group and phloretin treated CLP group. Sepsis was induced by CLP method. 50 mmol/kg phloretin was administered intraperitoneally in 2 equal doses immediately after surgery.
Results: It was observed that blood urea nitrogen (BUN) and tumor necrosis factor alpha (TNF-α) levels were dramatically increased in the CLP induced sepsis group (43.88±1.905 mg/dl, 37.63±1.92, respectively) when compared to the sham group. Moreover, tissue glutathione (GSH) and liver nuclear factor ĸB (NF-ĸB p65) transcription factor values were higher in CLP induced sepsis group. This elevation was considerably reduced in the phloretin treated CLP group. No significant differences were observed in serum creatinine and creatinine phosphokinase levels.

 

Conclusions: The present study suggested that phloretin, as a natural protective agent, acts against tissue damages introduced following the experimental sepsis induced model, likely caused by free oxygen radicals.

Biography:

Nazeeh Hanna is the Chief of Neonatology at Winthrop University Hospital. He is also the President-elect of the American Society for Reproductive Immunology. He is currently a Professor of Pediatrics, State University of New York at Stony Brook. He is an established Investigator who has international recognition for his work in reproductive immunology. His research track is focused in the area of “Developmental immunology and the impact of maternal exposure to environmental toxicants on preterm births”.

Abstract:

There is growing recognition that cytokines and inflammatory mediators present at the maternal-fetal interface play a fundamental role in regulating labor. IL-10 is an essential pro-pregnancy cytokine and therapies leading to its placental induction might be useful in preventing preterm deliveries. Although toxic in high concentrations, inhaled carbon monoxide (CO) in low concentrations can confer potent anti-inflammatory effects. Several pre-clinical and clinical studies have used CO as a therapeutic agent for a variety of vascular complications and sepsis; no published studies have evaluated the utility for this novel anti-inflammatory gas for preventing preterm delivery. The objective of this work is to investigate the role of CO in modulating infection-induced proinflammatory cytokine milieu in human placenta. Using placental explants culture system, samples from normal second trimester placentas were treated with LPS (250 ng/ml), 108 heat killed E. coli or 108 heat killed Urealyticum parvum with or without exposure to CO (250ppm) for 18 hours. Conditioned media were collected and analyzed for cytokines production using Bio-PlexTM array. Cultured tissues were analyzed by western blots for COX-2 and heme oxygenase-1 expression. To determine if CO exposure will induce cytotrophoblasts cell death, early pregnancy cytotrophoblasts cell lines (HTR8) were exposed to RA or CO (for 18 hours). Apoptosis was analyzed by FACS array. Our data indicate that CO effectively inhibits infection-induced proinflammatory mediators in second trimester placentas. Moreover, CO induced the pro-pregnancy cytokine IL-10 pointing to a potential role of CO in treatment of preterm labor.

Biography:

Marina M de Jesus Romero-Prado completed her PhD from Autonomous University of Madrid (UAM), Spain. She is a Molecular Biologist, Geneticist and works at Experimental and Clinical Therapeutics Institute at University of Guadalajara. She has published her discoveries in “Expression regulation of growth hormone gene and molecular and cellular research about biological potential of mesenchymal stem cells”. Her incursion as Leader in clinical protocols has served to bind the basic and applied research in complementary and translational medicine.

Abstract:

Introduction: In previous works, we demonstrated that dietary flavonoids have additional benefits on blood pressure, lipid profile, inflammation and electrocardiography parameters when they are added to antihypertensive pharmacological therapy.
Aim: Aim of this study is to analyze the possible role of Angiotensin Converting Enzyme (ACE) polymorphism (I/D) in response to the addition of dietary flavonoids (DF) to pharmacological antihypertensive therapy (AHT) in hypertensive young people.
Method: 37 male and 42 female patients with hypertension grade I (n=27) or II (n=52) received 425.8±13.9 mg gallic acid equivalents (GAE) from dietary flavonoids were added to AHT based on captopril (50 mg/day) or telmisartan (40 mg/day) during six months. Clinical registrations (SBP/DBP, BMI) were made during 15-days periods; lipid profile, hs-CRP and Leptin were measured in plasma at zero, one, three and six months; the ACE (I/D) polymorphism was determined by standard methods.
Results: Patients with AHT+DF compared to AHT showed differences in SBP (p<0.004), DBP (p<0.017), weight (p<0.022), BMI (p<0.028) and triglycerides (p<0.004); hs-PCR levels showed differences by ACE (I/D) polymorphism I/D vs. D/D (p<0.009). The genotypes D/D and I/I were associated to highest frequency of hypercholesterolemia and low HDL-C levels, respectively.
Conclusion: The response of FRD added to AHT has beneficial effects on BMI, BP, lipids and inflammation parameters and may be associated to ACE (I/D) polymorphisms.