22^nd World Congress on Toxicology and Pharmacology July 14-15, 2020 Kyoto, Japan

Biography:

Mahmoud Ibrahim Shoulkamy, PhD. Joined School of Medicine, Shenzhen University, China in 2019 as an Associate Research Scientist in Genome Stability & Disease Prevention lab. He also works as Associate Professor in Minia University, Egypt. He did his Ph.D. in Molecular and Cell Biology (DNA repair) at Hiroshima University in 2013, where he studying the induction and repair of DNA damage induced by various DNA damaging agents. He went on to do his post-doctoral work in Gene Chemistry lab, Hiroshima University, where he got 3 years special appointed Assistant Professor. His current work investigates the molecular mechanisms and signaling pathways of gastric cancer.

Abstract:

Anticancer drugs can concurrently generate three detrimental DNA lesions including DNA double-strand breaks (DSBs), DNA-protein cross-links (DPCs), and interstrand cross-links (ICLs) to varying degrees, and these lesions may differentially contribute to the toxicity of the drugs. However, no systematic studies have been performed about how much individual DSB, DPC, and ICL lesions contribute to cell killing upon treatment with anticancer drugs. Keeping this in mind, we treated HeLa cells with the equitoxic doses (LD20) of anticancer drugs and analyzed the induction of DSBs and DPCs. The association of ICLs with drug toxicity was assessed by the unique sensitivity of Chinese hamster ovary cells deficient in the xeroderma pigmentosum complementation group F gene. The results show that DNA lesions intimately associated with drug cytotoxicity vary significantly when HeLa cells are treated at the physiologically relevant doses. The critical cytotoxic DNA lesions are DSBs and DPCs for topoisomerase inhibitors (camptothecin and etoposide), DPCs for a DNA cytosine methyltransferase inhibitor (2’-deoxy -5-azacytidine), DPCs and ICLs for platinum drugs (cisplatin and oxaliplatin). Interestingly, cytotoxic DNA lesions are different for melphalan and mitomycin C although both are bifunctional alkylating agents. DSBs, DPCs, and ICLs are all associated with the cytotoxicity of melphalan, whereas ICLs alone are associated with the cytotoxicity of mitomycin C. Overall, our results provide a critical role of DPCs in anticancer drugs toxicity and raise the impact of DPC as a target for cancer therapies.

Biography:

Bhanu P S Sagar had completed his PhD from Jamia Hamdard, Post-doc from National Institute of Immunology and DSc in Alternative Medicine. He is presently the Director of Pharmacy College at IEC-GI & Former Vice-Chancellor of IEC University and has published 47 papers and presented 30 papers. He has presented two papers in “AAPS 2006 National Biotechnology Conference” in Boston, USA. He is evaluator for various international journals and also selected for “Marquis Who’s Who in Asia” and “Marquis Who’s Who in World”. He has received many awards and prime areas of research include Plant Tissue Culture, Phytochemical & Pharmacological investigations of natural products.

Abstract:

Xanthium strumarium L. is poisonous to mammals due its toxic principle which is a diterpenoid glycoside i.e. atractyloside found in the roots and seeds. It was thought worthwhile to carry out the hepatotoxic assessments and safety and toxicity evaluations of oral administration of atractyloside and methanolic extracts of X.strumarium L. in albino wistar rats. So, present investigation was undertaken with following objectives:

• To develop standardized protocols for Extraction, isolation, purification, chemical characterization and quantitative estimation of Atractyloside in Seeds / Roots.

• Hepatotoxic assessments of oral administration of atractyloside in albino wistar rats.

• To study the safety and toxicity evaluation of methanolic extract in albino wistar rats.

Xanthium strumarium Linn. roots and seeds was found to contain alkaloids, Free Amino acids, Anthraquinones, Reducing sugars, flavonoids, atractyloside, Phenolics, Steroids, Terpenoids, Resin, and Saponins. In the present investigation attempt was made to separate the atractyloside from seed and roots of the plant by using instant preparative thin layer chromatography (IPTLC) technique. The Purified atractyloside was chemically characterized by IR, Mass and NMR (Proton and Carbon NMR) spectral analysis. Atractyloside concentration was found to be 2.9 and 4.3 mg/ml in plant roots and seeds respectively using HPLC techniques.

During hepatotoxic assessment, atractyloside produced severe hepatotoxicity in albino wistar rats. Observations of the sub-acute and acute toxicity studies had clearly indicated that methanolic extract of X. strumarium had shown a narrow safety margin in animals. So, present investigation had indicated that atractyloside induces hepatotoxicity in rats. On the basis of subacute and acute toxicity evaluation studies, it was established that both atractyloside and methanolic extract of X. strumarium L. possess a narrow safety margin in experimental animals used in in-vivo experimental and preclinical pharmacological studies

Biography:

Ildikó Bata-Vidács has completed his PhD at the age of 31 in food sciences at Szent István University, Hungary. She works as a senior researcher at the Department of  Applied and Environmental Microbiology, Agro-Environmental Research Institute, Budapest, Hungary. She has published more than 30 papers and book chaptes in reputed journals, from which 15 are with impact factor, and has been serving as an editorial board member for Acta Alimentaria, a peer-reviewed international journal of food sciences.
 

Abstract:

Among mycotoxins, aflatoxins are the strongest natural genotoxins. Aflatoxin B1 (AFB1) is produced by Aspergillus flavus and A. parasiticus strains. Sterigmatocystin (STC) is a precursor of aflatoxin, a not well characterized mycotoxin with only few publications. For detoxification of already contaminated substances, specific bacteria might be the solution with toxin binding abilities. In our present projects, the AFB1 and STC binding ability of lactic acid bacteria is being studied.

For toxinadsorption studies stains of lactic acid bacteria were tested in MRS broth with 0.2 ppm AFB1 or STC. The binding abilities of the strains were determined after incubation from 10 min to 48 hours by measuring the toxin content of the centrifuged biomass by HPLC method with UV detection.

 The best AFB1 adsorption ability was found for L. plantarum TS23, L. paracasei MA2 and L. pentosus TV3 strains, binding nearly 10% of the toxin. Interestingly, for STC the binding rate was more than 20%. Neither AFB1 nor STC influenced the growth of bacterial strains at the tested concentration. It was found that 2 days of co-incubation was not required to bind the toxin, after 10 minutes, almost the same binding values ​​were obtained. Toxin binding was detected above 10⁷ cells/ml.

There is literature on AFB1 degradation by lactobacilli, but there is no published publication on STC binding. Beyond basic research, lactobacilli as active ingredients of a biological AFB1-binding preparation could be an important innovation in feeding.

This work was supported by the NVKP- 16-1-2016-0009 and OTKA K116631 projects.

Biography:

József Kukolya has completed his PhD in biological sciences at the Hungarian Academy of Sciences, Hungary. He works as head of the Department of Environmental and Applied Microbiology, Agro-Environmental Research Institute, Budapest, Hungary. He has published more than 100 papers and book chapters in reputed journals, from which 47 are with impact factor, and has been serving as chair for the Food-biotechnology Working Committee of the Hungarian Academy of Sciences, Hungary.        
 

Abstract:

Despite the structure similarity of aflatoxin B1 (AFB1) and sterigmatocystin (ST), the former is a much more harmful toxin according to the published data on their biological effects. In this research, the biological effects of ST and AFB1 were examined in two different biomonitoring systems.

For Escherichia coli based SOS-Chromotest, S9 rat liver P450 enzymes were used for producing genotoxic metabolic derivatives from AFB1 and ST. Equal concentrations of the toxins were measured for genotoxicity in intact form and after metabolic activation. The measured SOS-inducing potency of these toxins was almost the same: for intact AFB1, ST: 1.14 and 0.93;  for metabolized AFB1, ST: 74.08 and 74.14, respectively.

For the second biomonitoring system a newly developed test was used: S9-bioactivated AFB1 and ST were microinjected into zebrafish eggs. Mortality, sublethal effects, and DNA strand breaks were registered on the 5^th day of the treatment.

Metabolically activated sterigmatocystin caused the highest mortality and DNA strand breaks in all injected volumes. The sublethal symptoms on the embryos were the same for all treatments. The representative development dysfunctions were: moderately bent body, not well defined olfactory region, and irregular shaped lower and upper jaws.

Our findings contradict the assumption that AFB1 is a more potent genotoxin than ST. In the E. coli based SOS-Chromotest, the two toxins exert the same genotoxicities. Moreover, according to the newly developed zebrafish monitoring system, ST seemed even more toxic than AFB1. These results raise the demand for more complex biomonitoring systems for mycotoxin risk assessment.

This work was supported by the NVKP- 16-1-2016-0009 project.

Biography:

       Marzieh finished her high school in the national organization for development of exceptional talented (NODET) in 2014 and entered Tehran University of Medical Sciences (TUMS) in 2015. Currently she is a last year PharmD candidate and will acquire her PharmD within 6 months. Marzieh started researching at The Institute of Pharmaceutical Sciences (TIPS) in 2018 and started her thesis entitled “Protective effects of levosimendan on sodium arsenic-induced toxicity in rat’s pancreatic islets under in-vitro condition” in 2018; at the same time, started to write review articles in the field of GI toxicology/pharmacology and probiotic’s safety. Since 2019, Marzieh contributed in 7 papers (5 published and 2 submitted articles. She aims to continue her studies in PhD of toxicology very soon.

Abstract:

        Widespread use of probiotics and the presence of these microorganisms in human food-chain, established an argument against the safety profile of probiotics. Various case-reports, clinical trials and experimental studies have been mentioned different types of side-effects induced by the consumption of probiotics. Although previous studies reported beneficial impacts in alleviating the gastrointestinal (GI) problems, cardiovascular disorders and metabolic syndromes, the most at-risk groups of populations such as pediatrics, geriatrics, critically-ill patients are at higher risks  of the occurrence of some life-threatening or life-lasting adverse events. Bacteremia, fungemia, GI disorders, metabolic problems, extreme immune stimulations, seizure, Kawasaki disease and etc. have been associated with the use of probiotics. Moreover, due to the antibiotic resistance gene reservoir property of the GI tract, transference of the resistance genes among probiotics, human normal flora and pathogenic microorganisms endow probiotics to propagate antibiotic resistance genes globally.

Biography:

Shengjun zhang, 55 years old, senior engineer, he is the director of zhejiang environmental monitoring center, a premier environment protection serivice government agency. He has been subjected to environmental health and research work.

Abstract:

Mixed halogenated dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) are the class of contaminants due to plenty of congeners (4700 theoretically possible), limited analytical standards and complex environmental matrices. PXDD/Fs can be released from unintentional formation during industrial activities, and the toxicity potency of some PXDD/F congeners maybe greater than their corresponding chlorinated and brominated analogues. However, limited toxicological information on in vivo or in vitro exposure of PXDD/Fs is available. In the present study equimolar doses of environmentally relevant PXDF congeners (4-B-2378-CDF or 13-B-278-CDF) were added in fish feed (goldfish was given intraperitoneally) to zebrafish. After a 28 day exposure to two dose of 4-B-2378-CDF or 13-B-278-CDF (0.01 and 1 ng/g), the muscle tissue of zebrafish or goldfish was homogenized and analyzed. The results showed target compound was executed mostly while the recovery of control group was 98%. Four congeners of OH-PCDFs were identified and characterized in fish with authentic reference value by gas chromatography coupled with high resolution mass spectrometer (GC-HRMS). It’s noteworthy that this is the first finding PXDFs can be debrominated and hydroxylated in aquatic organism. Although the position of the hydroxyl groups cannot distinguished from the mass spectrometric fragmentation, the same debromination and hydroxylation pathways were observed both in 4-B-2378-CDF and 13-B-278-CDF. Such hydroxylation processes were well identified in fish for OH-PCBs. Our results revealed that in vivo exposure of PXDFs gave rise to plenty of OH-PCDFs in fish which is the first-hand data on metabolism of PXDFs and further studies are needed to evaluated metabolism or biotransformation mechanism in aquatic organism.

Biography:

Having completed her masters in Forensic Toxicology and with a degree in Analytical chemistry, she is currently pursuing her Ph.D in “Addiction Psychiatry” from National Drug Dependence Treatment Centre, All India Institute of Medical Sciences. She has been exploring various drug testing methods for toxicology samples to derive analytical conclusions.

Abstract:

Background: Ethyl Glucuronide (EtG) is a direct metabolite of alcohol. EtG in hair is proposed as a biomarker for assessment of long-term alcohol consumption.

Objective: To assess the association between Ethyl Glucuronide in hair with alcohol use.

Method: Using cross-sectional study design, ninety-one alcohol dependent patients (diagnosed as per International Classification of Diseases, Version-10) with last alcohol consumption within 24 hours were recruited after their consent. The subjective information included: socio-demographic details, alcohol use details and alcohol amount consumed in past three months (by beverage-specific quantity-frequency method). Three centimetre of hair from the posterior vertex region of the head was collected and analysed using gas chromatography–mass spectrometry. The obtained EtG values were compared and correlated with the amount of alcohol consumed.

Result: The mean age of the participants was 37.7 (SD:7.7) years. All participants used alcohol daily; country made liquor (CML) being the preferred beverage (51.6%). Mean quantity of alcohol consumed in past three months was 261.7 grams per person per day. The mean age of onset of daily alcohol consumption was 27.7 (SD:6.3) years and the mean age of onset of early morning drinking was 32.8 (SD:7.3) years. All hair samples showed hair EtG value higher than the cut-off (i.e. 30pg/mg). EtG values showed a positive correlation with the amount of alcohol consumed (p=0.05). Kruskal-Wallis test showed statistically significant differences between the EtG in hair and the quantity of alcohol consumed (Chi-square= 10.32, p<0.05, df=3).

Conclusion: Hair EtG can be positively used to indicate chronic alcohol consumption

Biography:

Mallika Srasri is a doctoral student in the Ph.D. program in Biology at Mahasarakham University, Mahasarakham, Thailand. She is working under the supervision of Assist. Prof. Dr.rer.nat. Panida Loutchanwoot and Assoc. Prof. Dr. Prayook Srivilai. Her research interests are in Endocrinology, Histology, Pharmacology, Toxicology. She holds a B.Sc. and a M.Sc. in Biology from Burapha University and Mahasarakham University, the largest Universities in the eastern and northeastern parts of Thailand, respectively. Her current dissertation involves the evaluation of biological action of phytoestrogens and endocrine disruptors on the functions of the pituitary-gonadal axis and lipid and thyroid metabolism in rat model.

Abstract:

Recent studies have reported that Pueraria mirifica (PM) exerts estrogenic-like effects in ovariectomized rats. However, lack of the estrogenic control groups in previous research studies were noted, and data about the biological mechanisms of action of P. mirifica on the pituitary-ovarian axis function and metabolic parameters in females with intact uteri and ovaries is still lack­ing. Adult female rats were allocated by randomization into 8 groups (n = 12/group). Groups I and II were vehicle control groups that were orally gavaged with olive oil and double distilled water (DDW), respectively. Groups III to VII were orally administrated respectively with 10, 100, 750, 1,000 and 1,500 mg/kg BW/day of PM’s root powder suspended in DDW. Group VIII was subcutaneously injected with 17β-estradiol (E2) at dose of 2 mg/kg body/day as the reference compound. Treatment period was 28 days. Serum levels of gonadal steroids and metabolic parameters were measured by chemiluminescent microparticle immunoassay and enzymatic colorimetric assay, respectively. PM did not affect relative weights of uterus and vagina, serum E2 and thyroid hormones levels. PM possessed E2-like properties in: 1) decreasing ovarian weight, 2) decreasing plasma levels of gonadotropins, and 3) reduction of serum lipids. This is the first report revealing that subacute administration of PM in intact female rats exerted weak estrogen-like actions on pituitary-ovarian axis function, lipid and thyroid metabolic parameters. PM therefore displayed the desired characteristics of a novel selective estrogen receptor modulator in adult female rats.

Biography:

Wafaa Mohamed El Sehly has completed her PhD at the age of 34 years from Alexandria University. She is a professor of Forensic Medicine and Clinical toxicology in Faculty of Medicine and Armed Faculty of Medicine Ministry of defense EGYPT. Also, she is the director of Quality Assurance Unit in Faculty of Medicine. She has published more than 35 papers in reputed journals and attended more than 50 national and 10 international conferences. She has included in the 2009 Edition of Who's Who in the World. She supervised many thesis, active member in different scientific associations and external reviewer in many scientific journals. She is the Advisory Representative of the Faculty of Medicine in front of the court in many criminal cases. She had Master quality mangement (MQM) at academy for science and technology and maritime transport.

Abstract:

Parabens are common ingredients in thousands of cosmetic and personal care products. Consumers of these compounds are frequently exposed via the skin, lips, eyes, oral mucosa, nails, and hair. Recently, parabens have been shown to act as xenoestrogens, a class of endocrine disruptors. They have been assessed for their metabolic activity as estrogen agonist that play a role in breast cancer development. The human breast adenocarcinoma cell line MCF-7 (Michigan Cancer Foundation-7) has served for over 40 years as a standard model for in vitro cancer research as well as estrogen and progesterone receptor science and is one of the key cancer cell lines used as a model for investigation of processes that impact patient care and provide a validated model system for assessing the ability of parabens to drive the growth of human breast cancer cells. However it is now recognized that MCF-7 is heterogeneous with respect to both the expression of hormone receptors and to the utilization of the signaling pathways linked to these receptors, differences that result in phenotypic heterogeneity. On the basis of a literature review, the National Institute for Health and Environment has investigated whether the three most commonly-used parabens (methyl-, ethyl- and propylparaben) can be considered as endocrine-disrupting substances. However, the available data from animal studies described in the literature do not provide sufficient information to be able to reach this conclusion.The present study aimed to study in vitro toxicological effects of methyl paraben on the behavior of MCF-7-McGrath human breast cancer cell lines.

Materials and Methods: MCF7 cells were obtained from ATCC and mantained as monolayer cell culture in RPMI phenol red free with 5% dextran charcoal stripped fetal bovine serum and incubated with estradiol (1*10^-8 M) and different doses of methyl parabens (4*10^-5 M, 6*10^-5 M, 1*10 ^-4M, 2*10 ^-4 M) for 7 days in 96 well plate for MTT assay. Inaddition to seeding in 6 well plate and incubated with parabens for 7 days to assess the gene expression of proliferation and apoptosis genes by real time PCR.

Results: No significant difference between the incremental doses of methyl parabens on MCF7 by MTT assay as a proliferative method. As regard the real time PCR of genes expression on going progress.

Conclusions: characterization and confirmation of the senstivity of MCF7 cell line in respect to the passage number, genetic diveristy of the cells, estrogen response growth curve and cross contamination..MTT assay isn’t necessarily a measuring proliferation assay

Biography:

Dr. Yousefipour received her PhD in Environmental Toxicology from Texas Southern University (TSU) in 2003. At the present time, she is a tenure full professor at TSU. Yousefipour has been studying the effect of environemtnal pollutants on cardiovascular system and has authored or co-authored more than 25 scientific papers in prominent journals. Yousefipour has been the recipient of Caroline Tum Sudan Professional Opportunity Award from American Physiological Society as well as several awards from TSU Research Week program. She is a member of several professional organizations including American Heart Association, American Physiological Society, and Society of Toxicology.

Abstract:

Nitric oxide (NO), an endogenous vasodilator, is a key regulator of basal vascular tone. Peroxisome proliferator activated receptor  (PPAR) ligand, clofibrate, has been reported to increase production of NO. Protein kinases C (PKC), a family of protein kinase enzymes, is involved in controlling the function of proteins through phosphorylation of hydroxyl groups of serine and threonine amino acid residues. Protein kinases A (PKA) is a cAMP-dependent protein kinase. There are evidence in support of clofibrate effect on NO production/availability independent of NO synthesis. Production of NO has been linked to protein kinases PKA and C-mediated signaling mechanisms. Therefore, we postulated that clofibrate-mediated increase in NO production might be attributed to PKA/PKC signaling pathway. We examined clofibrate mediated increase in NO production/availability in renal proximal tubular cells isolated from PPAR knockout (KO) mice and the role of PKA/PKC signaling pathways using PKA 14-22 and chelerythrine, PKA and PKC inhibitors, respectively. Effect of clofibrate on eNOS and iNOS gene/protein expression was examined. Our result indicated reduced NO production in PPAR KO mice compared to the WT. Addition of clofibrate enhanced NO production in both groups, which was abolished by L-NAME. Both PKC and PKA inhibitors reduced clofibrate-mediated NO production in both groups. Clofibrate increased eNOS and iNOS mRNA and iNOS protein expression in the KO but not in WT. Clofibrate did not affect PKA/PKC protein expression in either group. Our data suggest that clofibrate effect on NO production is through induction of iNOS gene and it is PPAR-independent mechanism.

Biography:

Mahmoud Ibrahim Shoulkamy, PhD. Joined School of Medicine, Shenzhen University, China in 2019 as an Associate Research Scientist in Genome Stability & Disease Prevention lab. He also works as Associate Professor in Minia University, Egypt. He did his Ph.D. in Molecular and Cell Biology (DNA repair) at Hiroshima University in 2013, where he studying the induction and repair of DNA damage induced by various DNA damaging agents. He went on to do his post-doctoral work in Gene Chemistry lab, Hiroshima University, where he got 3 years special appointed Assistant Professor. His current work investigates the molecular mechanisms and signaling pathways of gastric cancer.

Abstract:

Anticancer drugs can concurrently generate three detrimental DNA lesions including DNA double-strand breaks (DSBs), DNA-protein cross-links (DPCs), and interstrand cross-links (ICLs) to varying degrees, and these lesions may differentially contribute to the toxicity of the drugs. However, no systematic studies have been performed about how much individual DSB, DPC, and ICL lesions contribute to cell killing upon treatment with anticancer drugs. Keeping this in mind, we treated HeLa cells with the equitoxic doses (LD20) of anticancer drugs and analyzed the induction of DSBs and DPCs. The association of ICLs with drug toxicity was assessed by the unique sensitivity of Chinese hamster ovary cells deficient in the xeroderma pigmentosum complementation group F gene. The results show that DNA lesions intimately associated with drug cytotoxicity vary significantly when HeLa cells are treated at the physiologically relevant doses. The critical cytotoxic DNA lesions are DSBs and DPCs for topoisomerase inhibitors (camptothecin and etoposide), DPCs for a DNA cytosine methyltransferase inhibitor (2’-deoxy -5-azacytidine), DPCs and ICLs for platinum drugs (cisplatin and oxaliplatin). Interestingly, cytotoxic DNA lesions are different for melphalan and mitomycin C although both are bifunctional alkylating agents. DSBs, DPCs, and ICLs are all associated with the cytotoxicity of melphalan, whereas ICLs alone are associated with the cytotoxicity of mitomycin C. Overall, our results provide a critical role of DPCs in anticancer drugs toxicity and raise the impact of DPC as a target for cancer therapies.