Day 1 :
Keynote Forum
Alexei Basnakian
University of Arkansas for Medical Sciences, USA
Keynote: DNase/endonuclease network: a new target for mitigation of acute nephrotoxicity
Time : 10:00:10:55
Biography:
Alexei Basnakian received his PhD and DSc degrees from the Russian Academy of Medical Science, both in the field of DNA-degrading enzymes. He had postdoctoral trainings in molecular biology at the Harvard Medical School and in toxicology/cancer research at the National Center for Toxicological Research/U.S. Food and Drug Administration. Dr. Basnakian is a tenured Professor at the Department of Pharmacology and Toxicology, and Director of the DNA Damage and Toxicology Core Center at the University of Arkansas for Medical Sciences, and Research Career Scientist at the Veterans Hospital in Little Rock, Arkansas, USA. He is an author of 87 peer-reviewed papers and 14 reviews or book chapters. Dr. Basnakian is an Editorial Board member of four biomedical journals, and a member of NIH, AHA and VA grant study sections. His research interests are in DNases/endonucleases and DNA damage associated with toxicity, anti-cancer therapy, tissue injury and cell death.
Abstract:
Statement of the Problem: Deoxyribonucleases (DNases) universally induce irreversible cell death by fragmenting DNA in response to cell injury. All of the nine known cell death DNases are endonucleases. Despite that most of the DNase activity is used after cell death, a genetic inactivation of DNases provide protection of cells and tissues against DNA breaks induced by cytotoxic stimuli, and partially protect against tissue injury. Therefore, DNases act before the point-of-no-return in cell death, and can be potentially used as therapeutic targets for tissue protection against injury. Our studies identified two DNases, DNase I and EndoG, as being responsible for tubular epithelial toxicity during acute kidney injury induced by cisplatin, rhabdomyolysis or ischemia. However, inhibitors of DNases are not available. The purpose of this study was to identify DNase inhibitors, which might be used for mitigation of acute kidney injury.
Methodology & Theoretical Orientation: To identify DNase inhibitors, we have developed a high-throughput screening assay based on a proprietary fluorescent probe.
Findings: This assay allowed the identification of several new inhibitors of deoxyribonuclease I (DNase I), which were also active against two other DNases, endonucleases G (EndoG) and deoxyribonuclease II (DNase II). The DNase inhibitors were able to significantly protect kidney tubular epithelial cells in vitro and mouse kidneys in vivo against acute kidney toxicity induced by cisplatin, glycerol (rhabdomyolysis), or renal ischemia-reperfusion. The inhibitors showed no toxicity in vivo at 5x therapeutic doses.
Conclusion & Significance: DNases can be used as a therapeutic target for mitigation of toxic or hypoxic acute kidney injury. The identified DNase inhibitors or similar compounds have a great potential for tissue protection against toxic kidney failure. Considering that DNases are expressed and responsible for cell death in all tested cells, tissues and animal models, it is likely that the same compounds may be used for universal tissue protection against various injuries.
Keynote Forum
Stephanie Lora Sharp
The Glasgow Expert Witness Service Ltd, Scotland
Keynote: The Role of the Forensic Pharmacologist as an Expert Witness
Time : 11:10-12:05
Biography:
Dr. Sharp is a Forensic Pharmacologist. She has an M.Sci. degree in Pharmacology from the University of Glasgow, a Ph.D. in pharmacokinetics from the University of Dundee and Certificates in Civil and Criminal Law from the University of Cardiff. She specialises in drugs of abuse and the clearance of drugs from the body. She has prepared reports in many cases for a variety of legal firms in England, Wales, Ireland and Scotland She has been a research scientist for 8 years and has researched at the University of Cape Town in South Africa and the University of Dundee. Dr. Sharp is a co-director of the Glasgow Expert Witness Service Ltd. and is a registered expert witness with the Law Society of Scotland Directory of Expert Witnesses, a Professional Member of The Chartered Society of Forensic Sciences and a registered expert adviser on the National Crime Agency (NCA) database.
Abstract:
Forensic Pharmacology is a fascinating discipline internationally, covering everything from drink driving to the influence of drugs and alcohol in rapes and murders. Scotland is in the unenviable position of being the worst country in Europe for illicit drug-related deaths. The scope of my interest is from medical negligence to drugs of abuse such as new psychoactive substances. I take a particular interest in drugs of abuse and further to that the impact scientific expert evidence has in determining the outcome of cases and how this may be subverted by the judicial process.
I will be sharing specific case studies regarding the role of a scientist as an expert witness and the judicial outcomes of the cases. I will be addressing new psychoactive substances (“Spice”, synthetic cannabinoids, psychedelics, opioids) and medical misadventure resulting in death due to inappropriate therapeutic drug combinations.
From the position that I am in, I feel that it is of great importance to highlight the systems in place for illicit drug use and regulation as the differences in these systems may have dire consequences for the user and society in general. In my opinion, decriminalization of drugs of abuse in Scotland, the United Kingdom and, indeed, the rest of the World, will lead to a significant reduction in illicit drug-related harm as has been demonstrated in Portugal.
Keynote Forum
Ming-Tsang Wu
Kaohsiung Medical University, Taiwan
Keynote: Environmental melamine exposure and renal diseases
Time : 12:05-13:00
Biography:
Dr. Ming-Tsang Wu has completed his MD from Chung Shan Medical University in Taiwan and PhD from Harvard School of Public Health in the USA. He is a full professor in the Department of Public Health and the Director in Research Center for Environmental Medicine, Kaohsiung Medicine University, Taiwan. His major research interest is on the interactive effects of environmental and occupational exposures, genetic factors, and biomarkers on the health outcomes.
Abstract:
We are still exposed to low-dose melamine in daily-life environment, even after 2008 toxic milk food scandal. One of the main sources is the intake of melamine chemical from the migration of melamine-made tableware, when contacted with high-temperature soup/water. Our previous study has found that chronic low-dose melamine exposure is associated with the risk of renal stones in adults, but the data about the relationship between environmental melamine exposure and the risk of renal damage in humans is still lacking. In this talk, I will present our recent findings about that link from different susceptible populations and propose the mechanisms behind that.
Keynote Forum
Prakash Kinthada
National Institute Of Medical Science(NIMS) University, India
Keynote: Transition metal complexes/organometallic compounds as anticancer/anti HIV drugs or in pharmaceutical industry
Time : 09:30-10:30
Biography:
I am Prof. Dr. Prakash M.M.S Kinthada, a Professor in the Department Of Chemistry at National Institute Of Medical Science(NIMS) University, Jaipur, Rajasthan, India. Prior to this I was a Professor at Sri Vidyanikethan Engineering College, Jawahar Lal Technological University, Anantapur, A.Rangam Peta, Tirupathi, India. Earlier I was an Associate Professor in Chemistry at GIT, GITAM University, Visakhapatnam, India. I have recently returned from USA, where I was a NIH visiting fellow at KARMONAS CANCER RESEARCH INSTITUTE, Wayne State University School of Medicine. Earlier I was a Royal Society Visiting Scientist in the Inorganic chemistry laboratories at the University of Oxford, UK, working on “Transition metal complexes as Anticancer Drugs". Earlier I was a visiting fellow at the Department of Chemical Engineering and Applied Chemistry at Aston University, Birmingham. Prior to that I was a Nehru Centenary British Council Fellow in the organometallic laboratories at Imperial college of Science, Technology and Medicine, London, UK. Prior to that I was a CSIR Research associate in the Organometallic laboratories, Department of chemistry, Indian institute of Technology, New Delhi, India. I have published all my research in high impact international journals and Presented papers in International Conferences including American Chemical society Conferences. I have published 33 International publications and 31 international conference presentations including American Chemical Society conferences.
***I have been awarded a FRSC (FELLOW OF ROYAL SOCIETY OF CHEMISTRY by ROYAL SOCIETY OF CHEMISTRY, LONDON, UK.
*** My name has been included in THE DICTIONARY OF INTERNATIONAL BIOGRAPHY published by International Biographical center, CAMBRIDGE , ENGLAND , UK .
***I have been appointed as the DEPUTY DIRECTOR GENERAL OS THE INTERNATIONAL BIOGRAHICAL CENTER, CAMBIDGE, UK. And I have been Awarded 2000 OUTSTANDING INTELLECTUALS OF THE 21stCENTURY award by International Biographical center, Cambridge, England, UK. I have been awarded “TOP HUNDRED PROFESSIONALS OF THE YEAR-2011” by International Biographical center, Cambridge, England, UK. I have also received commemorative awards: Dictionary of International Biography Suite of Diplomas, Dictionary of International Biography, Medal of Inclusion and a CITATION OF MERITORIOUS ACIEVEMENTS, Pictorial Testimonial of Achievement and Distinction by International Biographical center, CAMBRIDGE, ENGLAND, UK. I have been awarded GOLD MEDAL OF INDIA, by AMERICAN BIOGRAPHICAL INSTITUTE, RALIEIGH, NORTH CAROLINA, USA. I have also been awarded DISTINGUISHED LEADER by AMERICAN BIOGRAPHICAL INSTITUTE, RALIEIGH, NORTH CAROLINA, USA. I have been made a MEMBER OF RESEARCH BOARD OF ADVISORS Conferred by AMERICAN BIOGRAPHICAL INSTITUTE, RALIEIGH, NORTH CAROLINA, USA. I have been awarded INTERNATIONAL PEACE AWARD AMERICAN BIOGRAPHICAL INSTITUTE, RALIEIGH, NORTH CAROLINA, USA. My name would be published in MARQUES WHO’s WHO IN THE WORLD.I have also been awarded JEWEL OF INDIA and a Certificate of Merit by Indian Solidarity Council, NEWDELHI, INDIA and I have been awarded BHARATH JYOTHI AWARD Rashtriya Gaurav Award by India International friendship Society, NEWDELHI, INDIA.
Abstract:
Cancer is a dreadful disease and any practical solution in combating this disease is of paramount importance to public health. Cancer patients have burdened by drug induced toxic side effects, and no turned to seek help from the complementary and alternative medicine hoping for a better cure. Research on Platinum based drugs and Non Platinum based drugs is a Multi-Million Dollar Industry in USA and there is every need to produce safe drugs for the cure of this monstrous disease. Flavonoids have a long history of use in traditional medicines in many cultures. The phytochemical, curcumin is one of the major dietary flavonoid, belonging to a group of flavonol, Curcumin is a natural polyphenol. It is highly potential molecule capable of preventing and treating various cancers. Various dietary chemo preventive agents, turmeric powder or its extract are broadly used as therapeutic preparations in Indian System of medicine. We provide a summarized synthesis and structural determination of Curcumin Oxime, Curcumin Thiosemicarbazone derivative of Gold (III) complex. The use of these analogs for prevention of cancer tumor progression and treatments of human malignancies. A pharmacologic agent for treating and/or preventing cancer, among other diseases and conditions, and particularly breast, prostate, and pancreatic cancer, in humans and animals. The novel pharmacologic agent is an isoflavonoid or isoflavonoid mimetic covalently attached to a cytotoxic pharmacophore that, preferably has the ability to conjugate with a metal salt to form a more potent metal complex, particularly a Au (III) complex and other complexes of Platinum, Palladium, Ruthenium, Copper etc.
My talk would mainly encompass different Transition Metal Complexes/Organometallic Compounds that are presently used as drugs, especially Anticancer and Anti-HIV drugs, apart from Anti-inflammatory, Antimicrobial, Antibacterial and diseases like Arthritis and Parkinson’s Disease etc. The talk would mainly focus on the use of Medicinal Chemistry and it’s application to Drug Design and Development in Pharmaceutical Industry , especially Transition Metal Complexes and Organometallic Compounds viz. Gold, Platinum, Palladium And Ruthenium apart from Copper, Cobalt, Iron, Nickel, Zinc, Cadmium etc.
The main emphasis of my talk would be on Different class of Ligands, their Schiff’s Bases and Transition Metal Complexes especially Au, Pt, Pd and Ru, with the main aim of designing, developing very novel small molecules, as possible and extremely potential candidates as Anti-cancer and Anti-HIV drugs. The talk would provide an overview of current programs being undertaken in our laboratories, especially focused on the development of potent ligands capable of recognizing Binding sites and diverse strategies employed by my group for elucidation of Anti-Cancer and Anti-HIV drug Leads to Circumvent the problem caused by Cis-Platin.
We have synthesized and characterized several phytochemicals from Traditional Medicinal Plants and isolated some phytochemicals and made the corresponding Oximes, Thiosemicarbazones and Substituted thiosemicarbazones as ligands and synthesized, characterized, structurally elucidated their Transition Metal Complexes especially with Gold, Platinum, Palladium, Ruthenium, Copper etc. and Studied their Anticancer Activity, Nuclease activity etc. and tested their potential as Anticancer Drugs.
The main aim of our extensive/preclinical Pharmaceutical development program is to investigate the use of these extremely novel small molecules-metal complexes/compounds of phytochemicals, flavanoids etc., which have very interesting structural features and properties and hence are excellent candidates as Anti-Cancer and Anti-HIV drugs .The main aim of our research is Design ,Development and Synthesis of Transition Metal Complexes/ Organometallic Compounds that would certainly help to bring this force of nature from BENCH to BEDSIDE and enhance Cancer Killing with less toxic effects and would certainly lead to initiation of clinical trials.
- Industrial & Occupational Toxicology
- Food Safety and Environmental Toxicology
- Pharmacology
Session Introduction
Sonia Shastri
University of Tasmania, Australia
Title: Therapeutics effect of idebenone in murine colitis
Biography:
Sonia Shastri is currently a PhD candidate at University of Tasmania, a recipient of Tasmanian Graduate Research Scholarship from University of Tasmania. She holds master degree in Pharmaceutical Science from the University of Tasmania and bachelors of pharmacy from Kurukshetra University, India. Her research focuses on investigating the efficacy of antioxidant drug in ulcerative colitis.
Abstract:
Idebenone, short chain Quinone, has been described as a potent antioxidant and mitochondrial electron donor. Its therapeutical potential has been described extensively in numerous pathological conditions ranging from neurodegenerative, neuromuscular to diverse metabolic conditions. There is also some emerging evidence that idebenone has some anti-inflammatory activity. Oxidative stress is one of the key players of the inflammatory cascade responsible for the initiation of Ulcerative Colitis (UC). Therefore, we investigated the anti-oxidative and anti-inflammatory properties of idebenone in dextran sodium sulphate (DSS)-induced mouse model of acute colitis. Acute colitis was introduced in female C57BL/6J mice by administering 2.5% of DSS in autoclaved water continuously for 7 days. Changes in body weight, disease activity index (DAI), colon length and histopathological parameters were evaluated and scored. Colonic contents of malondialdehyde (MDA), a marker of lipid peroxidation were also examined as a parameter of disease-associated redox state. Protein expression of the oxidative stress induced redox factor NAD(P)H dehydrogenase quinone-1 (NQO-1) was determined by western blot, while the levels of various pro-inflammatory cytokines were quantified using bioplex assay. Oral administration of idebenone at a dose of 200 mg/kg body weight significantly against body weight loss and improved DAI, colon length and histopathology. Idebenone also significantly reduced MDA content as well as pro-inflammatory cytokine levels such as IL-1α, TNF-α, G-CSF, GM-CSF, MIP-1α, MIP-1β, RANTES and EOTAXIN. Furthermore, idebenone upregulated NQO1 protein levels. These results suggest that idebenone could represent a promising therapeutic strategy to interfere with disease pathology in UC by inducing anti-oxidative and anti-inflammatory pathways.
- Toxicology
Session Introduction
Shikha Singh
University of Allahabad, India
Title: Studies on the assessment of pesticide induced stress and apoptosis in fresh water teleost Channa punctatus
Biography:
Shikha Singh is currently working as a Doctoral Fellow at University of Allahabad, India. She has completed her Masters of Science with cytogenetic specialization from University of Allahabad, India. She has presented ten oral posters in different international/national conferences organized in India. She has been awarded with Best Oral Presentation award for her work in Indian Science Congress Association. She also assists as resource person in various academic courses.
Abstract:
The application of chemical pesticides to agricultural land very often contaminate aquatic habitat which in turn causes detrimental effects to the aquatic biota particularly to the economically important non-target organisms like fish. The aim of the present study was to explore the impact of pesticides (triazophos, deltamethrin and their combination) on oxidative stress level in fish, Channa punctatus. The fishes were procured from local animal supplier of Allahabad, India and acclimatized in laboratory condition. The fishes were exposed to different concentrations of pesticides for 96 hours. The LC50 (Lethal Concentration) value for triazophos, deltamethrin and their combination were found to be 0.069 mg/l, 7.17 µg/l and 0.032 mg/l respectively. For the sub-lethal study, fishes were exposed to 5% and 10% of LC50 of pesticides for 96 hours. During the exposure period, the behavioral changes (i.e. opercular movement, surfacing) were observed. Immediately after exposure, the animals were sacrificed and blood and the key organs (brain, liver, kidney, gills and muscles) were collected for biochemical/stress enzymes assay and for apoptotic studies. In the blood parameters, TLC and DLC showed significant change in counts as compared to control with increased rate of apoptosis. In the stress related enzyme activity such as SOD, CAT, GST and levels of GSH and LPO (Lipid Peroxidation) significant changes were recorded with increase in concentration of pesticides. From our study conclude that, the dose dependent exposure of pesticides may impose detrimental threat to the fish population.
SALAKO N. OLATUNJI
Federal Institute of Industrial Research Oshodi, Nigeria
Title: RESEARCH ON ANTIDOTE OF CHEMICAL WEAPONS KNOWN AS SODASULPHANECOBLAMIN
Biography:
Has expertise in quantum physics, also on determination of numerical value of dimension on physical quantities. Root mean square velocity and molecule velocity of all chemical elements which is never done before. stoichiometry and periodic properties table that shows the” INTRINSIVE AND EXTRINSIVE PROPERTIES” of all chemical elements. Determination of Molecular Mass and Formula for Air. Computational Mathematics and Application of Small organic Molecules. Antidote of chemical mass weapon (2, 3, 7, 8 - Tetrachlorobenzo-p-dioxin). Critical cGMP and ICH regulations for Pharmaceutical Laboratory. Pollution or environmental remediation studies, anthropogenic effect on petroleum. Synthetic of compound for biological evaluation. Synthetic of helium compound, which is another source of sun. Research on Oil Dispersant. Production of antidote of Cyanide Poisoning.
Abstract:
SodaSulphanecobalamin (Na4S5 CoC69N15H89O26) is an antidote for Chemical weapons, which detoxify and decentralized the toxic substances in any chemical based threat mainly, classical chemical agent threat categories include vesicant or blister agents (e.g., sulfur mustard), blood agents (e.g., cyanide), respiratory agents (e.g., phosgene), and nerve agents (e.g., GA or Tabun, GB or Sarin, GD or Soman, and VX) as well as lung damaging agents (Chlorine, diphosgene). It dissociate the toxic components in each chemical weapons, either nerves agent, blister agent or mustard gas to a nontoxic substance when administered and doesn't have any adverse effects unlike Atropine (which has little effect on nicotinic effect, such as muscle twitching, flaccidity) and other antidotes been tested for neutralizing or countermeasures for a particular chemical based threat. It displaces the Cyanides to a free toxic compound, thiocyanocobalamin .It removes the burns when the sulfur mustard is been contacted through skin, and eye The antidote (SodaSulphanecobalamin) which is sulfur drug group (H-S) bends the mustard makes the anditodal removes mustard from the body, of which can be used as treatment for Organic Arsenical. It also added the amide group of protein when used. However, recent studies shows that this antidote can serve as a replacement for the antidote of Orange agent (2, 3, 4, 7-tetra chlorobenzodioxin) which displaced millions of Vietnam Citizens during the World War II and displaces chlorobenzo to sodium benzoate and saline. Though Mercury (I) Oxalate is been used for this antidote for the orange agent, but we all know that Mercury is highly toxic and poisonous to the human .Nerve agents developed in the 1930s and 1940s were stockpiled during the Cold War. More recently, nerve agents have been used in the Iran–Iraq War in the 1980s, the Japanese terrorist attacks by the Aum Shinrikyo cult in 1995 and attacks in Syria in 2017.
Recently, the Salisbury Nerve attack on March 4th 2018,when SodaSulphanecobalamin is been used for nerves agent antidotal , it dissociates organophosphate to phosphoric acid which helps in metabolism of the body.
(Na4S5 CoC69N15H89O26) is produce by dissolution of hydroxocobalamin with the decomposition of Sodium nitrite and Sodium thiosulfate, then treated with the acidified Sodium bicarbonate, which led to a faster return to baseline mean arterial pressure compared with sodium nitrite with sodium thiosulfate; however, there was no difference between the antidote combinations in mortality, serum acidosis, or serum lactate (TERTSodium1,2-diithiosulphite-3,4diiintroso Co-α(α-5,6diimethlybenzylmizazonly)co-β-hydroxocobalamin)
NO + HOcbl +2NaoH + NO2 +3Na2SO4 + Na2S5 2Na2S2O3 + 2NaNO2 + 4NaOH +HOSCb1 +SO2 (g) ------------------------- Na4 (S2O3)2 (NO2)2 C62H87SCON13O16P
This Research helps to develop the concepts, therapeutic regimens and procedures for the management of chemical warfare agent casualties; developing diagnostic and prognostic indicators for chemical warfare agent casualties; and developing life-support equipment for definitive care of chemical warfare agent casualties.
The most efficient and reliable way to treat chemical weapons is by using SodaSulphanecobalamin. It is non-carcinogenic, non-mutagenic and non-teratogenic compound which is composition doesn’t has any toxicity and health effect when administered. It can also be used as any chemical based threat
Rishikesh K. Tiwari
University of Allahabad, India
Title: Toxicological evaluation of chlorpyrifos, cypermethrin and their combination in earthworm and their impact on Acetylcholinesterase
Biography:
Rishikesh Kumar Tiwari (Doctoral Fellow): Presently working as a Doctoral fellow with Prof. Ravi S. Pandey, Biochemistry Laboratory, Department of Zoology, University of Allahabad, Mr. Rishikesh K. Tiwari has completed his M.Sc. with cytogenetics specialization from University of Allahabad, India. He has presented ten oral/poster in different International/National Conferences organized in India besides ten research/review articles in National/International journal repute and one book chapter in USA based publishing house. He has attended one International workshop and assisted as resource person in various academic course(s).
Abstract:
The increasing applications of pesticides in the agricultural fields have adverse impact on flora and fauna of the soil ecosystem. The role of earthworms in the agricultural practices is well known as they immensely contribute in increasing the quality and fertility of soil. So, it acts as a bioindicator for the ecotoxicological analysis of pesticide induced soil pollution. Therefore, the present study was aimed to explore the impact of chlorpyrifos (an organophosphate; OP), cypermethrin (a pyrethroid) and their combination (chlorpyrifos + cypermethrin) on earthworm, Eudrilus eugeniae. E. eugeniae were exposed to different concentrations of pesticides for 48 h by paper contact toxicity method. The LC50 for commercial grade chlorpyrifos, cypermethrin and their combination were determined as 0.165, 0.066 and 0.020 μg/cm2 respectively. To assess the sub-lethal effect of these pesticides, E. eugeniae were exposed to 5% and 10% of LC50 pesticides for 48 h. Alterations in morpho-behavioural patterns such as coiling, clitellar swelling, mucus release, and bleeding followed by fragmentation of body in earthworms were observed following exposure. Acetylcholinesterase (AChE) activity was assayed in different regions of body segment which exhibits significant (p < 0.05) decrease in AChE activity particularly in pre-clitellar region followed by clitellar and post clitellar regions and in comparison, to whole body. The decreased AChE activity with increasing concentration of pesticides indicates the effect at neuronal level which apparent from the behavioural changes. Therefore, from the present findings it can be concluded that long term exposure to these pesticides could lead to severe and irreparable effects on biochemical mechanisms of earthworms.
- Experimental Toxicology and Pathology
Biography:
Abstract:
Omega-3 fatty acids offer several health benefits. In present investigation, hepatoprotective potential of omega-3 fatty acids in the form of flax oil and fish oil was assessed against repeated alcohol dosing in male albino Wistar rats. Hepatic injury was induced by administering 30 % alcohol (1ml/100g b.w./day, p.o). Flax oil and fish oil (500mg/kg b.w./day, p.o) were administered to hepatotoxicity induced rats. Biochemical parameters were analyzed from serum and liver tissue. The expressions of fatty acid binding protein 1 (FABP1), peroxisome proliferator activated receptor gamma (PPARγ), sterol regulatory element binding protein 1 (SREBP1), nuclear factor kappa β (NF-kβ) and tumor necrosis factor alpha (TNF-α) genes from liver were assayed by semi-quantitative polymerase chain reaction. Administration of flax oil or fish oil prevented hepatic damage with marked improvement in hepatic function and normalization of lipid profiles in serum and liver. These interventions normalized oxidative stress through improvements in levels of anti-oxidant enzymes and oxidative stress markers. Expression of genes such as FABP1, PPARγ were downregulated and SREBP1, NF-kβ and TNF-α were upregulated in alcohol induced hepatotoxic rats while treatment with flax oil and fish oil showed improvement in these gene expression. Histological analysis showed normal hepatic architecture in flax oil and fish oil treated animals. The flax oil was found could protect the liver against alcohol-induced liver toxicity and oxidative stress. However, further clinical studies are required to assess the safety and benefits of flax oil in human beings.
- Applied pharmacology
Session Introduction
Ben C. Valdez
UTMDACC, USA
Title: Pharmacological optimization of the conditioning regimen for hematopoietic stem cell transplantation
Biography:
Dr. Ben Valdez obtained his PhD in Biochemistry at Louisiana State Univ. He did his post-doctoral training at Baylor College of Medicine in Houston, TX and became an Assistant Professor. His laboratory cloned the genes and corresponding cDNAs for RNA helicase II/Gu α and β and discovered their functions. His lab identified the functions of treacle, encoded by the TCOF1 gene, in the expression and methylation of pre-ribosomal RNA. In 2005, he transferred to the Dept of Stem Cell Transplantation and Cellular Therapy, UT MD Anderson Cancer Center where he is now an Associate Professor. His current research focuses on the identification of safe and efficacious conditioning regimen for hematopoietic stem cell transplantation for patients with hematological disorders. He conceptualized and proved the efficacy of combined DNA alkylators, nucleoside analogs, and epigenetic modifiers in leukemia, lymphoma and multiple myeloma cells, and proposed a model called the “loop of death” to explain the cytotoxic synergism of these drugs. He developed an assay for cellular efflux of chemotherapeutic drugs which is relevant to understanding drug interactions. Using this assay, Dr. Valdez discovered the differential effects of HDAC inhibitors on cellular drug transporters which have tremendous implications for using epigenetic modifiers in combination chemotherapy. The results of his pre-clinical studies have been used as bases for several clinical trials at UT MD Anderson Cancer Center
Abstract:
Statement of the Problem: Hematopoietic stem cell transplantation is an effective treatment for a variety of hematological disorders. Its success partly depends on the optimization of the pre-transplant conditioning regimen.
Methodology & Theoretical Orientation: To identify an efficacious regimen, we exposed cells to different drug combinations, analyzed their cytotoxicity and identified their molecular mechanisms of interaction using various techniques.
Findings: We have shown the synergistic cytotoxicity of DNA alkylating agents (AA) and nucleoside analogs (NA) in leukemia and lymphoma cells and proposed a mechanistic model called the “loop of death”. Exposure of cells to a nucleoside analog initiates DNA damage resulting in chromatin remodeling and makes genomic DNA more susceptible to DNA alkylation. DNA damage response is then activated and the loop of DNA damage, chromatin remodeling, and DNA alkylation continues until the tumor cells commit to apoptosis. Using this model and the [AA+NA] combination as a backbone to identify drugs that may further enhance its anti-tumor activity, we hypothesized that epigenetic modifiers would amplify the loop of death. Indeed, inhibitors of histone deacetylases (HDACi) and DNA methyl transferases (DNMTi), which facilitate relaxation of chromatin, were found to be synergistic with [AA+NA]. Since active DNA repair may contribute to decreased efficacy of these drug combinations, we also examined the inclusion of DNA repair inhibitors such as olaparib. Addition of olaparib to [AA+NA] caused significant apoptosis by activation of the DNA-damage response, inhibition of PARP activity and DNA repair, production of reactive oxygen species and depolarization of the mitochondrial membranes.
Conclusion & Significance: Our pre-clinical studies have been translated to the clinic and results from some of our clinical trials will be presented. Overall, our pre-clinical and clinical results suggest that the conditioning regimen for HSCT may be optimized by combining drugs that provide synergistic cytotoxicity based on their molecular mechanisms of action.
- Industrial & Occupational Toxicology
Session Introduction
Katarzyna Miranowicz-Dzierżawska
National Research Institute, Poland
Title: Differences between cytotoxicity of preservatives used in cosmetic industry determined on consecutive passages of senescent diploid human lung fibroblasts in vitro
Biography:
Katarzyna Miranowicz-Dzierżawska works in Laboratory of Toxicology, a part of the Department of Chemical, Aerosol and Biological Hazards in the Central Institute for Labour Protection – National Research Institute. She was graduated from the Faculty of Pharmacy (specialization: pharmaceutical analysis) of the Medical University of Warsaw and she prepared her dissertation (Ph.D.): “The evaluation of interaction between chosen organic solvents” at the Collegium Medicum of Jagiellonian University, Cracow. The main area of her professional interest are problems of human in the working environment and the toxicity of chemical substances as well as methods of estimating the toxicity of substances in vitro. She was also engaged in preparation of documentation of maximum allowable levels of occupational exposure and characteristics of hazardous substances in the work of the Interdepartmental Committee mandated with updating and verification of the Threshold Limit Values (TLVs) for agents harmful to human health.
Abstract:
Statement of the Problem: Cell culture system could be a useful model for aging-related changes. The aim of the study was to assess whether there are differences between the results of determination of preservatives cytotoxicity obtained on senescent cells in different age.
Methodology & Theoretical Orientation: Experiments were conducted to determine the cytotoxicity of four preservatives: methylparaben, propylparaben, 2-phenoxyethanol and benzalkonium chloride on subsequent passages of senescent human lung CCD-8Lu (ATCC CCL-201TM) fibroblasts. The tests were carried out in passages no. 10 / 18. Xenobiotics cytotoxicity was evaluated using two cell viability assays: MTT assay, determining metabolic activity of cells, and NRU assay, assessing the integrity of cell membranes. The IC50 values were used as the main measure for comparing the cytotoxicity of tested compounds.
Findings: The results showed that the preservatives can be ranked according to the increasing cytotoxic potency towards the tested human diploid lung fibroblasts: 2-phenoxyethanol methylparaben propylparaben benzalkonium chloride. Older cells became less susceptible then the younger ones with cytotoxic effects of the xenobiotics tested in the majority of cases.
Conclusion & Significance: The passage number of diploid human lung fibroblasts had an important impact on the susceptibility of cells to preservatives. The test of the integrity of cell membranes (NRU) seems to be more appropriate to assess the cytotoxic effect of the investigated preservatives on diploid fibroblasts in different ages, which may be related to the mechanism of action of these compounds.
Funding: This paper has been based on the results of a research task I.N.13 carried out within the scope of the fourth stage of the National Programme Improvement of safety and working conditions partly supported in 2017–2019 — within the scope of research and development — by the Ministry of Science and Higher Education/National Centre for Research and Development.
- Analytical Toxicology
Biography:
Dr Raafat Abdeldayem is an associate professor at Mansoura University, Egypt.
Abstract:
Objectives: the abuse of drugs can have serious ramifications on a person’s physical health, mental health, and overall well-being. Aim of the work is to determine the prevalence of some drugs among patients from the laboratory point of view.
Methods: the sample size for this study was five hundred patients with acute poisoning by some drugs of abuse. In this study all patients were subjected for detection of drugs of abuse in urine by EMIT system and Gas Chromatography / Mass Spectrometry (GC/MS) for confirmation of the obtained results.
Results: the study revealed that the percentages of positive urine samples by Enzyme Multiplying Immunoassay Technique (EMIT) confirmed by Gas Chromatography / Mass Spectrometry (GC/MS).
Conclusion; presence of these drugs has a serious effect on man health, consequently his environment.
Recommendations: it is recommended that public health intervention aimed at preventing drug use among inhabitants should be designed to raise awareness about the negative effects of drug abuse.
- Toxicology and Risk Assessment
Session Introduction
Nyandwi Ramadhan
University of Burundi, Burundi
Title: Acute intoxication cases reported in emergency unit at University Teaching Hospital of Kamenge (CHUK)
Biography:
NYANDWI Ramadhan has a bachelor degree in Pharmacy and a Master of Sciences in Pharmacology and Toxicology. Currently he is a PhD student in Toxicology at University of Burundi Doctoral School.
Abstract:
Statement of the Problem: Burundi is a country in East Africa Region, with a population around 11 million over an area of ​​27,834 km2; without access to the sea but having a large shore on Lake Tanganyika. It is surrounded by the Democratic Republic of Congo (DRC) to the west, Rwanda to the north, and Tanzania to the southeast. Health, hygiene, education and transport, are missing the necessary investments for development. There is no specialized center for intoxication management in the Burundian territory, qualified personnel and technical facilities in the poisoning management are also inadequate. On the other hand, individual or massive intoxications are frequent, especially during ceremonies, and voluntary or involuntary poisonings also exist. The overall objective of this work is to identify acute intoxications and its management at CHUK emergency department, and data of this study will be used to advocate for the implantation of at least one center for poisoning management in Burundi..
Methodology: This is a retro-prospective study of acute intoxication cases in emergency department of CHUK from June 2017 to August 2018. Data in this study have been collected from records and an interview of patients after informed consent agreement.
Findings: Preliminary results showed that from June 2017 to August 2018, 39 cases of acute intoxication were reported to the emergency services, including 9 cases of children under 6 years; with 56.4% and 43.6% of men and women respectively. The causes of poisoning were mainly food, chemicals products and drugs with 53.8%, 23.1% and 15.4% respectively. Other minor intoxication causes were gas and venom with 5.1% and 2.6% respectively. Treatment of intoxication cases was either palliative or symptomatic based on patient history.
Conclusion & Significance: Poisoning cases in Burundi need to be treated based on toxicological tests evidence however there’s neither toxicological laboratory nor qualified personnel. Symptoms of intoxication are not always recognized and treatment is inadequate, so that recommendations are made to national, regional and international body to avail at least one intoxication center.
Sumaira kanwal
COMSATS institute of information technology, Pakistan
Title: Toxic effects of chromium metal releasing from tanneries on plants, soil, water, effluent and urine of workers
Biography:
Dr. Sumaira Kanwal has completed her PhD at the age of 27 years from Kongju national University Korea and postdoctoral studies from Samsung Medical center. After getting her degree she is working as a faculty member in COMSATS institute of information technology (One of the leading Universities of Pakistan. She has published more than 25 papers in reputed journals and has been serving as editorial board member of various journals. Her main field of interest is Neurology and neuromuscular disorders.
Abstract:
Toxic Effects of Chromium Metal on plants, soil and water in Vicinity of Tannery Industries and on the urine of labor working in tannery Located in Sahiwal have been seen. In this regard, data has been taken from two tanneries (Yousaf Tannery and Qamar Tannery). Results show that the metal has very toxic effects on plant, soil and water and hence polluting the environment. Effluents from the tannery contain a large amount of Cr and have hazardous effects on plants therefore a very little flora has been found near tanneries. Results also show the toxic effects of waste on soil. This waste has been damaged the characteristic features of soil by reducing its fertility, damaging its color and increasing its pH that it is not suitable for the growth of plants. Water near the tannery has noticeable amount of Cr according to results. However, the effect of Cr on the urine of workers has not remarkable effects.
- Food Safety and Environmental Toxicology
Session Introduction
Zhi-Zhong Guan
Guizhou Medical University, China
Title: Pathogenesis and intervening measures of the coal-burning type of endemic fluorosis in China
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 and the president in the International Society of Fluoride Research. He has published more than 500 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 fluorosis and a vast array of pathological changes in whole bodies. Coal-burning type of endemic fluorosis is the severest one, which was confirmed in China in 1970’s. This type of endemic fluorosis is primarily induced by fluoride-contamination from food and air indoor due to the emitted smoke during burning coal (containing high amount of fluoride) in opened stoves for drying food in Autumn harvest and warm oneself in Winter by the residents in the areas. In Guizhou Province of China, about 15 million of people live in such areas of coal-burning type of endemic fluorosis. Among the population, 10 millions are suffered from dental fluorosis and 0.8 million skeletal fluorosis. Since 1980, an efficient strategy relating the integrated control has been carried out for eliminating the disease in the areas of China. First, the adapted stoves without pollution from burning coal have been set up, which brings the significant decline of fluoride contamination on food and air indoor; second, education relating the harm of fluoride pollution from coal burning on body to the residents has been carried out. After taking the strategy for many years, the numbers of the patients with dental or skeletal fluorosis has been significantly decreased, indicating that the coal-burning type of endemic fluorosis in China has been efficiently controlled. On the other hand, the basic researches have been carried out to understand the pathological changes and the molecular pathogenesis. The damages of excessive fluoride on multiple organs of the patients besides the skeletal and dental fluorosis have been found. In addition, we suggested earlier that the increased level of free radical resulted from fluoride might the main mechanism in the damages of multiple organs or systems by fluorosis, which has been subsequently confirmed by large number of investigates. In our results, as compared to control cases, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) and the expressions of SOD and GST mRNAs as well as the raised malondialdehyde (MDA) level were significantly decreased in the blood of the population living in the areas with severe coal-burning endemic fluorosis. The changes of hepatic and renal functions were detected in the residents living in the areas of endemic fluorosis. Interestingly, the health conditions of the residents in the endemic fluorosis area has been greatly improved after several years of the integrated control. Furthermore, the clinic treatments for the patients with dental and skeletal fluorosis have been performed by the dentists and surgeons, the imaging diagnosis has been improved by the imaging doctors in our hospital, in which the better results have been achieved. The pharmaceutical drugs for the treatment to the patients with chronic fluorosis have also been investigated and the preclinical results have been obtained in our group. Importantly, it is necessary to notice that we should take a long-period of integrated control for efficiently eliminating the hazard of coal-burning type of endemic fluorosis.
- Toxicology
Session Introduction
Gulrana Khuwaja
Jazan University, Saudi Arabia
Title: Mechanistic approach on the combined toxicity of selenium and tellurium in rat neuroendocrine centers
Biography:
Currently Dr. Gulrana Khuwaja is working as Assistant Professor in the Department of Pharmaceutical Chemistry, College of Pharmacy Jazan University. She got Ph.D. in Chemistry from Aligarh Muslim University, India. She has one patent and published more than 25 papers in reputed and peer-reviewed international journal with a sum of more than 40 impact factor. Her research has been cited in more than 1,000 citations. She was honoured three times with "best poster presentation awards" at Jazan University. Her supervised students also got three times best poster presentation award at Jazan University. She is a lifetime member of “Indian Academy of Neurosciences”. She is also engaged as a principal investigator in an approved project in Jazan University.
Abstract:
Selenium and tellurium are widely used in so many industries including steel, rubber, electronic, ceramic, glass, zinc, arsenic, cadmium, aluminum, copper, tin, thallium, daylight lamps, electronics, photocells, silicon semiconductor devices, manufacture photographic exposure, solar cells, xerography, red or black glass, pigments in plastics, paints, dyes, enamels, inks, textiles, rubber, photographic emulsions, and petroleum (Taylor, 1996, Se-Te, 2013). Earlier Islam et al. (2002, 2004) and his group (Kaur et al., 2003 a, b) has reported its neurotoxicity on lipids and oxidative stress parameters in the brain. Extending the earlier work of Islam group, we further studied the toxicity of Se and Te on neuroendocrine centers in rats brain. This will be the first report of its kind. The male Wistar rats treated with 1/20th of LD50 of sodium tellurite (4.15 mg, orally), 0.3 mg/kg sodium selenite (i.p) and the half combination of these metals i.e., sodium tellurite (2.075, orally) + sodium selenite (0.15 mg/kg, i.p) for a period of 15 days. On day 16, the animals were sacrificed and brains were taken out to dissect the hypothalamus, pituitary and pineal gland. Each brain part was weight and homogenized in 10 mM Tris-HCl, pH 7.4 to give 5 % homogenate. The homogenate was used for the assay of lipid peroxidation and activity of SOD. The supernatant (15,000 g x 20 min at 4 °C) was used for the other enzymatic and non-enzymatic assays (GSH GPx, GR, GST, Catalase, Caspase-3, and Caspase- 9.
Biography:
Abstract:
The goal of the study was to determine the role of aconitase in dysfunction of the dopaminergic system in Mn-exposed rats. Further, this study aimed to investigate the protective effects of nutrient metal mixture (Calcium, Zinc and Iron) against Mn-induced neurotoxicity. Male pups were exposed to Mn (6mg/Kg body weight) through intraperitoneal injection and the nutrient metal mixture as 0.02% by a single gavage together with Mn separately given from PND 15 to PND 28. The results showed that Mn exposure significantly decreased the synaptosomal dopamine levels and mitochondrial aconitase and monoamine oxidase enzyme activities in the cortex and cerebellum of PND 29, PND 60 and 3 months age groups of rats. Mn treatment significantly down-regulated the expression levels of aconitase, caspase-3, and caspase-9 in the cortex and cerebellum whereas the expression level of tyrosine hydroxylase was up-regulated at PND 29 and downregulated in PND 60 and 3 months age groups of rats. In silico molecular docking results reveal that Mn showed stable binding capacity with aconitase compared to iron binding capacity. Furthermore, histopathological observations showed that marked neuronal degeneration and congestion of blood capillaries in the cerebellum whereas cortex exhibited focal area of vacuolation with marked hemorrhagic lesion and edema following exposure to Mn. However, supplementation of nutrient metal mixture attenuated the Mn-induced impairments in apoptotic markers and mitochondrial enzymes with subsequent restoration of dopamine levels. In conclusion, our findings indicate that decreased activity of aconitase may disrupt mitochondrial apoptotic pathway which can lead to exacerbation of oxidative stress and contribute to neurotoxicity. Further the data suggest that nutrient metal mixture provides protection against Mn-induced neurotoxicity.
Shanmugam Thangapandiyan
Bharathiar University, India
Title: Sulforaphane prospectively rescue Arsenic induced hepatotoxicity and apoptosis through PI3K/Akt/Nrf2 signaling pathway
Biography:
Dr.Shanmugam Thangapandiyan (National Postdoctoral Fellow): Presently working as a Postdoctoral fellow with Prof. Ramesh, Unit of Toxicology, Department of Zoology, Bharathiar University, Tamilnadu, India. He has completed his PhD in heavy metal toxicity and its phytoremediation field from Annamalai University, India. He has received Gold medal in UG and Silver medal in P.G Zoology with best outgoing student award in 2009 and 2011. He has presented many research papers in different International/National Conferences organized in India and received best oral presentation award recently. He has published many research/review articles in National/International reputed journal with high impact factor and one book chapter in UK based publishing house. He has recently awarded by Indian government with National Postdoctoral Fellowship (2017-2019) in the field of Toxicology at Bharathiar University, Coimbatore, India.
Abstract:
The present investigation was intended to assess the defensive capacity of sulforaphane (SFN) against arsenic (As) prompted hepatotoxicity by enactment of PI3K/Akt/Nrf2 interceded flagging pathway. For this reason, male Wistar rats were haphazardly disseminated into 6 gatherings of 8 rats each: control, Arsenic (5mg/kg BW), SFN in addition to Arsenic (20, 40, 80 mg/kg BW; 5mg/kg BW). The arsenic-incited oxidative harm was affirmed by a noteworthy (p<0.05) increment in the levels of ALAD, and in the Arsenic focus and additionally exhaustion in cell reinforcement content. Besides, Arsenic medications essentially (p<0.05) expanded the expert apoptotic marker (Bax) and DNA harm, with diminished Nrf2 protein in charge of liver insurance. Be that as it may, pretreatment with SFN essentially (p<0.05) diminished the levels of ALAD, Arsenic focus, and brought cancer prevention agent proteins into typical levels. This was expert by hindrance of apoptotic markers by means of actuation of PI3K, Akt and Nrf2 interceded flagging pathway as clear from histology, western smudging and PCR procedures. In summary, SFN treatment shield the hepatocytes in Arsenic treated gatherings proposing a version of liver poisonous quality by means of PI3K/Akt intervened Nrf2 flagging pathway.