MMSL, 2022 (vol. 91), Suppl.1

INTERDISCIPLINARY TOXICOLOGY CONFERENCE TOXCON 2022Supplementum

Kamil Kuca

MMSL 2022, 91(88):1-3  

Dear Friends and Colleagues,It is my pleasure to welcome you at Interdisciplinary Toxicology Conference TOXCON 2022 which is organized in Hradec Kralove, the Czech Republic (August 29 to September 1, 2022).Along with a great scientific program, the participants will be able to enjoy Hradec Kralove, a magnificent historic city, founded in the 13^th century. Hradec Kralove, known as the „Salon of the Republic“, is a center of modern Czech architecture with theaters, galleries, concert halls, colleges and universities. Hradec Kralove (with about 100,000 inhabitants) is the home of the University of Hradec...

BENCHMARK DOSE APPROACH IN EVALUATION OF IN VIVO AChE-REACTIVATING EFFICACY OF PROMISING EXPERIMENTAL OXIMES K203 AND K027Meeting abstracts

Evica Antonijevic Miljaković, Kamil Musilek, Kamil Kuča, Danijela Đukić Ćosić, Marijana Čurčić, Aleksandra Buha Djordjevic, Zorica Bulat, Biljana Antonijević

MMSL 2022, 91(88):4  

Benchmark dose (BMD) approach, as an advanced statistical methodology for dose-effect analysis in toxicological research (1) was used to quantitatively characterize in vivo efficacy of two experimental bispyridinium oximes K203 and K027, following promising findings on their low acute toxicity and potential to reactivate acetylcholinesterase (AChE) inhibited by organophosphorus (OP) pesticides and nerve agents in vitro and in vivo (2). Immediately after DDVP challenge (75% LD₅₀, s.c.), male Wistar rats were treated with oxime (0/1.25/2.5/5/25/50% LD₅₀, i.m.). Erythrocyte and diaphragm AChE activity was determined...

PHARMACOLOGICAL MODULATION OF M-TOR IN ANIMAL MODEL OF NAFLD/NASHMeeting abstracts

Mahak Arora, Nikolina Kutinová Canová, Zuzana Pavlíková

MMSL 2022, 91(88):5  

Non-alcoholic Fatty Liver Disease (NAFLD) promotes to Non-alcoholic Steatosis Hepatitis (NASH), liver cirrhosis and cancer. However, there is no specific clinical treatment for NASH. Previously, we screened in vitro model for novel drug candidates towards NAFLD/NASH. The mTOR inhibitor was found to significantly alleviate palmitic acid-induced lipotoxicity in hepatocyte culture. Therefore, the aim of presented study was to investigate the effect of non-specific mTOR inhibitor (KU-0063794) when given orally in dietary model of NAFLD/NASH. To develop NAFLD and NASH in vivo, male mice C57Bl6J were fed with Atherogenic High Fat Diet (AHFD),...

CELL GROWTH ON TiO₂ NANOTUBES AND Ti FLAT SUBSTRATES COATED WITH METAL OXIDES USING ATOMIC LAYER DEPOSITIONMeeting abstracts

Jana Bacova, Jan Capek, Hanna Sopha, Raul Zazpe, Jan M. Macak, Tomas Rousar

MMSL 2022, 91(88):6  

Titanium is one of the most widely used materials for medical and dental implants due to its resistance to body fluid effects, low ion release, great tensile strength, flexibility, and high corrosion resistance. Despite its promising properties, titanium implants tend to be encapsulated by fibrous tissue in vivo and show a lack of osseointegration, which can lead to infections and implant failure (Hansson; 1983). To improve the surface properties of materials, the atomic layer deposition method is used, where the surface of the material is modified with one or more uniform layers of metal oxide, which directly correlates with the...

CHALLENGES IN STUDYING NANOTOXICITY IN VITROMeeting abstracts

Jana Bacova, Petr Knotek, Jan Capek, Pavlina Majtnerova, Ludek Hromadko, Jan M. Macak, Tomas Rousar

MMSL 2022, 91(88):7  

The broad use of nanomaterials in material science, medicine or industry has implied the request to evaluate their biological effects. In vitro cellular models provide a suitable approach to study those effects, but it can be difficult to ensure valid and repeatable experimental conditions for proper setting of biological testing. Indeed, a number of physicochemical parameters (e.g. type of dispersion, aggregation, colloid stability, agglomeration) can influence the obtained results. Thus, the topical goal of our study was to provide a complete view on testing of commonly used nanomaterial, i.e. titanium dioxide nanoparticles, in cultured cells.

THE ROLE OF OXYSTEROLS AND THEIR SIGNICIFANCE IN PANCREATIC CANCER IN VITROMeeting abstracts

Stepan Balatka, Alzbeta Spalenkova, Marie Ehrlichova, Pavel Soucek

MMSL 2022, 91(88):8  

Oxysterols are 27-carbon derivatives of cholesterol formed by enzymatic, as well as non-enzymatic, oxidation of cholesterol. They participate in cholesterol metabolism and influence many cellular processes, but they are also involved in the etiology of different diseases, including cancer. Previous studies found that oxysterols influence anti-cancer treatment in vitro, e.g., the presence of different oxysterols modulates the activity of doxorubicin, 5-fluorouracil, docetaxel, or cisplatin.The aim of this study is the analysis of the role of nine oxysterols in pancreatic cancer in vitro. Two human pancreatic cell lines, Paca-44 (mutated...

NEUROBEHAVIORAL CONSEQUENCES OF CHRONIC ADMINISTRATION OF POTENTIAL ANTIDEPRESSANT SMe1EC2M3 IN ANIMAL MODEL OF DEPRESSIONMeeting abstracts

Alexandra Ballóová, Romana Koprdová, Alexandra Reichová, Ján Bakoš, Mojmír Mach

MMSL 2022, 91(88):9  

Depression is becoming the most common psychiatric illness worldwide. Its etiology is not fully understood, but the monoamine theory is supported by antidepressant mechanism of action that modulates monoaminergic systems. Known antidepressants have various side effects, so there is a need to search for new therapeutics. Our previous study revealed an antidepressant effect after acute pyridoindole derivative SMe1EC2M3 treatment (1).We studied the effect of chronic administration of the SMe1EC2M3 under stressed conditions induced by chronic mild stress (CMS) procedure in Sprague-Dawley male rats (n=72). From day 8th of the CMS, we intraperitoneally...

EFFECT OF IBUPROFEN AND DICLOFENAC ON SELECTED INDICES IN COMMON CARP (CYPRINUS CARPIO)Meeting abstracts

Jana Blahová, Přemysl Mikula, Veronika Doubková, Zdeňka Svobodová

MMSL 2022, 91(88):10  

A significant global problem of contamination of the aquatic ecosystem is the abundance of pharmaceuticals entering the aquatic environment as a result of their widespread use. An important group of drugs commonly detected in surface waters are non-steroidal anti-inflammatory drugs (e.g. ibuprofen and diclofenac). The aim of the present study was to evaluate the potentially negative effects of diclofenac and ibuprofen administered in feed on selected biochemical and haematological parameters of common carp (Cyprinus carpio). The test organisms were exposed to various concentrations of these non-steroidal anti-inflammatory drugs at concentrations...

MONOTERPENES MODULATE THE ACTIVITY AND EXPRESSION OF DETOXIFICATION ENZYMES IN HUMAN LIVERMeeting abstracts

Iva Boušová, Michaela Šadibolová, Gabriela Svobodová, Martin Ambrož, Ehiofomwan Ameze Omwanghe, Filip Čečka

MMSL 2022, 91(88):11  

Monoterpenes, volatile molecules widely distributed in plants, are used in folk medicines, pharmaceutical and food industries, and cosmetics. Most terpenoids easily enter the human body by oral absorption, skin penetration, or inhalation leading to measurable blood concentrations. Numerous biological activities, including antitumor activity, of monoterpenes have been reported. On the other hand, some monoterpenes were reported to exhibit toxic effects in various organs of human organism, mostly in liver (1). The monoterpenes are also able to modulate the activity and/or expression of some drug-metabolizing enzymes. Present research was carried out...

TOWARDS THE HIGH-THROUGHPUT ASSESSMENT OF THYROID HORMONE SYSTEM DISRUPTORSMeeting abstracts

Ondrej Brozman, Puja Kumari, Liu Runze, Tereza Rysava, Petra Mikusova, Jiri Novak, Klara Hilscherova

MMSL 2022, 91(88):12  

The thyroid hormone regulation is a vital and complex process for proper organism function that involves multiple organs across species. A disruption of the thyroid hormone system (THS) by endocrine disruptors (EDs) can be linked with adverse effects such as developmental and autoimmune disorders. However, THS has been rather neglected, even though EDs have been gaining attention recently. Currently, the H2020 ERGO project aims to develop a battery of high-throughput in vitro bioassays based on molecular initiating events (MIEs) in the adverse outcome pathway network connected to THS disruption (tAOP) to narrow the knowledge gap.The thyroid...

CONGENITAL CYTOMEGALOVIRUS INFECTION - A PROBLEM OF PAST, PRESENT AND FUTUREMeeting abstracts

Ingrid Brucknerová, Dušan Doboš, Michal Dubovický, Mojmír Mach, Eduard Ujházy, Jana Brucknerová

MMSL 2022, 91(88):13  

The Cytomegalovirus (CMV) pass through placenta is connected with consequences in prenatal as well as postnatal phase of development. Newborns can be asymptomatic, can have mild or even life-threating symptoms with serious long-term sequels. All CMV infected newborns are at risk of long-term neurodevelopmental problems and sensorineural hearing problems.The aim of the work: To analyse prenatal and postnatal characteristics, clinical and laboratory findings, results of investigations in the group of 11 newborns with congenital CMV infection, who were hospitalized at Neonatal Department of Intensive Medicine between January 1st 2012 and March 31st,...

EVALUATION OF CYTOTOXIC EFFECTS OF FIVE BISPHENOL ANALOGS (A, AF, B, F, S) IN PROSTATE CELL LINES LNCaP AND PC3Meeting abstracts

Bujňáková Mlynarčíková Alžbeta, Scsuková Soňa

MMSL 2022, 91(88):14  

Bisphenol A (BPA), a widely used plastic additive with proven endocrine disrupting properties, has been previously linked to reproductive system disorders and tumors. Due to such harmful effects, its use has become restricted but other bisphenol (BP) analogs have been introduced as replacements for BPA usage in many applications. However, little is known about their biological actions or about similarities with the actions of the prototype BPA. The present study used the human prostate cell lines: androgen-unresponsive PC3 cells and androgen-responsive LNCaP cells, to examine effects of bisphenols AF, S, F and B, in comparison to BPA. We focused on...

THE EFFECT OF KETAMINE, AN NMDA-RECEPTOR ANTAGONIST, ON GASTRIC MYOELECTRIC ACTIVITY IN EXPERIMENTAL PIGSMeeting abstracts

Jan Bureš, Jaroslav Květina, Věra Radochová, Veronika Knoblochová, Stanislav Rejchrt, Martin Vališ, Ondřej Soukup, Darina Kohoutová

MMSL 2022, 91(88):15  

Preclinical studies in experimental pigs are carried out mostly under general anaesthesia. Ketamine is commonly used for introduction to anaesthesia. However, concerns exist, whether ketamine, an NMDA-receptor antagonist, influences gastric motor function. The aim of this study was to investigate porcine gastric myoelectric activity by means of electrogastrography (EGG). Seventeen female animals (mean weight 36.2±3.8 kg) were enrolled. Drugs used as an introduction to anaesthesia were: Group A (n=5): medetomidine 0.1 mg/kg i.m.; butorphanol 0.3 mg/kg i.m.; midazolam 0.3 mg/kg i.m.; Group B (n=6): azaperon 2.2 mg/kg i.m.; Group C (n=6): ketamine...

THE EFFECT OF SINGLE AND REPEATED DOSES OF RIVASTIGMINE ON GASTRIC MYOELECTRIC ACTIVITY IN EXPERIMENTAL PIGSMeeting abstracts

Jan Bures, Chrysostomi Christina Tsianou, Jaroslav Kvetina, Ilja Tacheci, Vera Radochova, Darina Kohoutova, Stanislav Rejchrt, Veronika Knoblochova, Martin Valis, Jana Zdarova Karasova, Ondrej Soukup

MMSL 2022, 91(88):16  

Rivastigmine is a pseudo-irreversible cholinesterase inhibitor used for therapy of Alzheimer´s disease and non-Alzheimer dementia syndromes. In humans, rivastigmine can cause significant gastrointestinal side effects that can limit its clinical use. The aim of this study was to assess the impact of rivastigmine on gastric motor function by means of electrogastrography (EGG) in experimental pigs. Six experimental adult female pigs (3-month-old; mean weight 30.7±1.2 kg) were enrolled into the study twice and created two experimental groups. In group A, a single intragastric dose of 6 mg rivastigmine hydrogen tartrate was administered in the morning...

RISK OF MERCURY FROM FISH AND FISH PRODUCTSMeeting abstracts

Milena Bušová, Vladimír Bencko

MMSL 2022, 91(88):17  

Mercury exists in the environment as elemental, metallic mercury, inorganic mercury and organic mercury.  Elemental and inorganic mercury released into the atmosphere from combustion of fossil fuels, mining, smelting and various industrial activities. In the aquatic environment is mercury deposited to sediments where is transformed into the main organic form methylmercury. Mercury methylation occures in the aquatic environment due to microorganisms metabolism as sulfite reducing bacteria.  The toxicity of mercury in humans or animals depends on its chemical form. Elemental mercury is volatile, gastrointestinal absorption of inorganic mercury is between...

TOXIC PRODUCTS OF SARS-CoV-2 AND OTHER NON-TOXIC MARKERS IN COVID-19 PATIENTSMeeting abstracts

Milena Bušová, Vladimír Bencko, Milan Tuček, Věra Očenášková, Romana Pospíšilová

MMSL 2022, 91(88):18  

Coronavirus disease COVID-19 is highly infectious disease caused by SARS-CoV-2 virus as a novel coronavirus led to pandemic. Due to fast transmission COVID-19 has become a global problem. The virus is spread by aerosol from infected people and persists in the air for a long period. SARS-CoV-2 affects the lungs, but it can also affect digestiv or cardiovascular systems, can attact the brain, damage vessels and can lead to neurological manifestation. COVID-19 has several clinical symptoms and can lead to multiorgan dysfunction and death. On the other hand, in some infected persons COVID-19 can take place asymptomatic. Due to the risk of rapid spread...

STUDYING CADMIUM NEUROTOXICITY IN VITROMeeting abstracts

Jan Čapek, Jiří Handl, Pavlína Majtnerová, Tomáš Roušar

MMSL 2022, 91(88):19  

Cadmium is a toxic transition heavy metal commonly found in the environment and its occurrence is mainly conditioned by agricultural and industrial production. Increased exposure to cadmium, especially because of its accumulation in organisms, causes damage of kidney, liver, and bones. Intracellularly, there are proteins, metallothionines, that are actively involved in the detoxification of cadmium by its uptake. In response to increased ROS production after exposure to cadmium, the Nrf2 protein, which modulates glutathione synthesis, is activated (1). The activation rate of Nrf2 protein depends on the concentration of cadmium in a certain time interval...

BEHAVIORAL OUTCOMES OF MATERNAL STRESS AND PERINATAL MIRTAZAPINE TREATMENT IN RAT OFFSPRINGMeeting abstracts

Kristína Csatlósová, Mireia Viňas-Noguera, Kristína Belovičová, Michal Dubovický

MMSL 2022, 91(88):20  

Untreated depression during pregnancy has wide spectrum of negative effects on the mother and the child. Recently, the rising numbers of depression in pregnant women were followed with a steep rise of antidepressant use. Mirtazapine is an atypical antidepressant generally considered to be safe to use during pregnancy and lactation.Aim of our study was to investigate the effect of maternal stress and effect of perinatal mirtazapine treatment on the behavior of rat offspring. Adult female Wistar rats were randomly assigned to stress and control groups and subjected to three weeks of chronic unpredictable stress schedule and mated with males....

THE ROLE OF UDP-GLYCOSYLTRANSFERASES IN XENOBIOTIC-RESISTANCEMeeting abstracts

Diana Dimunová, Petra Matoušková, Radka Podlipná, Iva Boušová, Lenka Skálová

MMSL 2022, 91(88):21  

Uridine diphosphate sugar-utilizing glycosyltransferases (UGTs) are an enzyme superfamily that catalyzes glycosyl residues transfer from activated nucleotide sugars to acceptor molecules. In addition to various endogenous compounds, numerous xenobiotics are substrates of UGTs. As the glycosides formed are generally less active/toxic and more hydrophilic than aglycones, UGTs effectively protect organisms from potentially harmful xenobiotics. Therefore, increased UGTs expression and/or activity improves the protection of the organism and may contribute to the development of individuals that become more resistant to certain xenobiotics. While the function...

IN VITRO DECONTAMINATION EFFICACY OF NEWLY DEVELOPED DECONTAMINATION MEANS ON NERVE AGENTSMeeting abstracts

Alzbeta Dlabkova, Marek Matula, Aneta Markova, Jan Marek

MMSL 2022, 91(88):22  

The aim of the presented work was to evaluate the decontamination efficacy of newly developed decontamination agents based on surfactants with hydroxyl functional group.Sarin and VX were selected as representative nerve agents (NA). The ability to accelerate the catalytic hydrolysis of the NA was assessed by the pH value measurement using an automatic burette. The hydrolysis of NA in a contaminated solution leads to a decline of pH value due to the formation of O-alkyl methylphosphonic acids (MPAs). The ability of tested surfactants to penetrate through the skin and their rinsing effectivity was observed using modified Franz-type of glass diffusion...

ANTIDEPRESSANTS IN TREATMENT OF MATERNAL DEPRESSION: RISKS AND BENEFITSMeeting abstracts

Michal Dubovicky, Kristina Belovicova, Mojmir Mach, Ingrid Brucknerova, Mireia Vinas Noguera, Eduard Ujhazy, Kristina Csatlosova

MMSL 2022, 91(88):23  

Depressive disorder is a serious mental illness whose incidence is constantly increasing in developed countries. About 20% of pregnant women suffer from maternal depression. Both untreated and treated maternal depression represents risk factor for development of fetus and newborn. The maternal hormones, such glucocorticoids, have been reported to be altered in response to a maternal challenging environment. These molecules cross the placenta and reach the fetus, altering the neurodevelopmental pathways in the fetus that may affect the proper brain functioning, leading to an increased risk for neurodevelopmental disorders. Antidepressants used to treat...

ABSENCE OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN 2 INCREASES THE PLASMA CONCENTRATIONS OF BILE ACIDS IN RATS WITH ESTROGEN-INDUCED CHOLESTASISMeeting abstracts

Fatemeh Alaei Faradonbeh, Hana Lastuvkova, Jolana Schreiberova, Milos Hroch, Zuzana Nova, Martin Uher, Petra Hirsova, Petr Pavek, Stanislav Micuda

MMSL 2022, 91(88):24  

Multidrug resistance-associated protein 2 (Mrp2) is the crucial transporter for the biliary secretion of anionic compounds. The genetically determined absence of this transporter may occur in humans, causing conjugated hyperbilirubinemia and increased risk of intrahepatic cholestasis of pregnancy (ICP). The ICP threatens fetuses with adverse pregnancy outcomes due to increased bile acids (BAs) plasma concentrations. This study aimed to characterize BAs metabolomics in Mrp2 deficiency and ICP. Cholestasis was induced in Mrp2-deficient and wild-type rats by ethinylestradiol as a model of ICP. BAs were analyzed in plasma, bile, and stool to describe their...

PREDICTION OF DRUGS’ SIDE EFFECTS IN SILICOMeeting abstracts

Jakub Fibigar, Tomáš Kučera

MMSL 2022, 91(88):25  

The goal of this project is to create algorithm and software solution for prediction of drugs’ side effects. The algorithm is based on calculations of interactions between active substances and known macromolecules.Methods of molecular docking and reverse molecular docking are used there. Each exanimated drug substance is docked into binding site of each macromolecule of sc-PDB database while the interaction between them is calculated. A set of decoys is selected from the ZINC database based on chemical properties. Decoys are docked into binding site of each macromolecule as well as exanimated drug substances. The docking results of exanimated...

SYNTHESIS OF PURINE DERIVATIVES WITH ANTIMYCOBACTERIAL ACTIVITYMeeting abstracts

Vladimir Finger, Martin Novak, Jan Kubes, Jan Korabecny, Jaroslav Roh

MMSL 2022, 91(88):26  

Tuberculosis (TB) is one of the top 10 causes of death worldwide from a single infectious agent. The World Health Organization (WHO) estimated 10 million new cases and 1.5 million deaths from TB in 2020 (1). Some strains of mycobacteria causing TB show numerous resistances to first-line drugs (isoniazid /INH/ and rifampicin) and to second-line drugs (fluoroquinolones, amikacin, bedaquilin, etc.). The development of new anti-TB drugs with new mechanism of action is necessary to improve TB therapy and to fight against resistant TB as well.We screened our in-house library of small molecules for their therapeutic potential and identified compound...

THEORETICAL ASSESSMENT OF THE PERFORMANCES OF COMMERCIAL OXIMES ON THE REACTIVATION OF ACETYLCHOLINESTERASE INHIBITED BY THE NERVE AGENT A-242Meeting abstracts

Tanos Celmar Costa Franca, Marcelo C. Santos, Fernanda D. Botelho, Arlan S. Gonçalves, Kamil Kuca, Eugenie Nepovimova, Samir F. A. Cavalcante, Antonio L. S. Lima

MMSL 2022, 91(88):27  

The nerve agents of the A-series are relatively recent chemical weapons with no antidote available yet (1). Once inside the human body, those chemicals act similarly to the classic nerve agents, by binding to the catalytic residue Serine 203 (Ser203) of human acetylcholinesterase (HssAChE) and thus preventing the proper function of this enzyme. However, there is no experimental evidence yet if the current antidotes for intoxication by nerve agents are also capable of restoring AChE inhibited by the nerve agents of the A-series. In order to launch some light on this issue, we used computational techniques (molecular docking, molecular dynamics...

PHYTIC ACID- PROTECTIVE OR HAZARDOUS COMPOUND?Meeting abstracts

Veronika Frýbortová, Štefan Šatka, Lenka Jourová, Pavel Anzenbacher, Eva Anzenbacherová

MMSL 2022, 91(88):28  

Phytic acid (IP6) is the most abundant inositol phosphate in nature present in plants as well as in mammalian cells, thus, IP6 is common part of human diet. IP6 has been considered for a long time as an antinutritional component due to its ability to bound minerals and affect their bioavailability in gastrointestinal tract (1). On the other hand, the protective effects of IP6 have been reported in pathological conditions including neurodegenerative diseases, cardiovascular diseases and cancer, likewise, a hepatoprotective effect has been observed (2). Cytochromes P450 (CYPs) are key enzymes involved in the metabolism of 70-80% of all...

IN VITRO ASSESSMENT OF POTENTIAL GENOTOXIC EFFECT OF THE ACETAMIPRID-BASED INSECTICIDEMeeting abstracts

Martina Galdíková, Simona Koleničová, Beáta Holečková, Jana Halušková, Viera Schwarzbacherová

MMSL 2022, 91(88):29  

Neonicotinoid insecticide acetamiprid is a part of relatively frequently used commercial formulations such as Mospilan 20SP or newly developed Carnadine, Kestrel and others. The popularity of these insecticides lies in their ease of handling and high efficacy in treating canola, corn, potatoes and apple trees. However, the possibility that pesticide products could also affect non-target organisms still needs to be taken into account. For this reason, the aim of our work was to assess the possible cytotoxic and genotoxic effects of acetamiprid-based insecticide Mospilan 20SP, which is one of the well-known commercially available formulations. Conventional...

PHENOTHIAZINE-TACRINE HETERODIMERS: PURSUING MULTITARGET DIRECTED APPROACH IN ALZHEIMER’S DISEASEMeeting abstracts

Lukas Gorecki, Elisa Uliassi, Manuela Bartolini, Jana Janockova, Martina Hrabinova, Vendula Hepnarova, Lukas Prchal, Lubica Muckova, Jaroslav Pejchal, Jana Z. Karasova, Eva Mezeiova, Marketa Benkova, Tereza Kobrlova, Ondrej Soukup, Sabrina Petralla, Barbara Monti, Jan Korabecny, Maria Laura Bolognesi

MMSL 2022, 91(88):30  

Since 2002, no clinical candidate against Alzheimer’s disease has reached the market; hence, an effective therapy is urgently needed. We followed the so-called “multitarget directed ligand” approach and designed 36 novel tacrine phenothiazine heterodimers which were in vitro evaluated for their anticholinesterase properties. The assessment of the structure−activity relationships of such derivatives highlighted compound 1dC as a potent and selective acetylcholinesterase inhibitor with IC₅₀ = 8 nM and 1aA as a potent butyrylcholinesterase inhibitor with IC₅₀ = 15 nM. Selected hybrids,...

DIFFERENCES IN THE BIOLOGICAL EFFECTS OF BACTERIAL AND SYNTETIC MELANINMeeting abstracts

Jiří Handl, Pavlína Majtnerová, Jan Čapek, Tomáš Roušar

MMSL 2022, 91(88):31  

Melanins are heterogeneous polymeric dark pigments colored in black with relatively diverse properties, functions and rather non-defined structure. Many of commercially available melanins used in scientific studies have been produced synthetically or isolated from natural sources (1, 2).We studied two types of melanin, i.e. commercially available synthetic melanin (SM) and biotechnologically obtained bacterial melanin (BM) from Bacillus thuringiensis. The topical aim of our study was to estimate the biological effects of both melanins in the neuroblastoma SH-SY5Y cell line. After melanin treatment (0-200 μg/mL), cell viability, glutathione...

ATOPIC DERMATITIS MODEL OF HUMAN KERATINOCYTES  IN VITROMeeting abstracts

Jiří Hanyk, Alena Rajnochová Svobodová, Jitka Vostálová

MMSL 2022, 91(88):32  

Atopic dermatitis (AD) is a chronic inflammatory skin disease, which is still not fully understood. Crucial roles in the pathogenesis play Th2 immune response dysregulation and epidermal barrier alterations. Defects of this skin barrier have been considered in the initial step of AD development. Inflammatory skin conditions AD have a negative wide-ranging impact on a patient’s life quality. However, testing methods and/or treatment options for this disease are unsatisfactory nowadays.To study the anti-inflammatory effect of substances on AD pathogenesis we established inflammatory models by stimulating HaCaT cells with tumor necrosis factor-α...

EFFECTS OF ENROFLOXACIN AND MARBOFLOXACIN TO SELECTED AQUATIC ORGANISMSMeeting abstracts

Barbora Havelkova, Ivona Toulova, Miroslava Beklova

MMSL 2022, 91(88):33  

Enrofloxacin and marbofloxacin are two veterinary fluoroquinolones used to treat severe bacterial infections. The release of fluoroquinolones in the environment is mainly due to the direct discharge of aquaculture products and the excretion in urine and feces of livestock animals. It results in the contamination of soil, surface water, sediment, ground water and biota.We focused on acute and reproductive effects of enrofloxacin and marbofloxacin, in particular. Assessment of the impact of selected antibiotics on important representatives of the aquatic environment. The aim of this study was to investigate the chronic toxicity of the antibiotics...

NOVICHOK: BASIC KNOWLEDGE OF BIOCHEMICAL PROPERTIESMeeting abstracts

Vendula Hepnarova, Martina Hrabinova, Lubica Muckova, Petr Jost, Lucie Junova, Jakub Opravil, Alzbeta Dlabkova, Daniel Jun

MMSL 2022, 91(88):34  

In recent years, the most mentioned nerve agents by the public are A–agents, so-called Novichoks. The official chemical structures of these new organophosphates have never been published. The possible structures were introduced by Vil Mirzayanov in 2009 (1), however, they do not correspond with structures published by Hoenig (2).One type of Novichok was evaluated in our laboratory and its physical-chemical and biological properties were compared to well-known structures of nerve agents such as sarin or VX. Inhibition kinetics of human acetylcholinesterase and butyrylcholinesterase was determined. Further, the ability of standard oxime nerve...

EFFECT OF POLYSTYRENE MICROPARTICLES ON EMBRYONIC LIFE STAGES OF ZEBRAFISH (DANIO RERIO)Meeting abstracts

Aneta Hollerova, Denisa Medkova, Pavla Lakdawala, Jana Blahova, Nikola Hodkovicova, Martin Faldyna, Zdenka Svobodova

MMSL 2022, 91(88):35  

Plastic pollution is a global problem caused by an excessive use of this material, its high resistance in the environment and poor waste management. In the environment, larger-sized plastic particles may be transformed into smaller particles, so-called microplastics (< 5 mm), which have been discovered in the bodies of various organisms, across all trophic levels of the aquatic environment (Provencher et al., 2017). Effects of microplastics on fish embryos are described as malformations, changes in behavior and swimming ability, early hatching, increased mortality and decreased heart rate (Bhagat et al., 2020). However, these negative effects must...

HUMAN PRECISION-CUT INTESTINAL SLICES AS A MODEL TO STUDY DRUG-MEDIATED INDUCTION OF INTESTINAL ABCB1 AND CYP3A4Meeting abstracts

Martin Huličiak, Tereza Hradecká, Tereza Mazurová, Pavla Podhorná, Lukáš Červený, Ivan Vokřál

MMSL 2022, 91(88):36  

Drug-mediated induction of the intestinal ABCB1 and CYP3A4 is a clinically relevant phenomenon associated with reduced drug bioavailability. Well-established human models to assess the induction are currently missing, so drug regulatory authorities provide no recommendations to test in vitro/ex vivo drugs' induction activity. Human precision-cut intestinal slices (hPCIS) contain cells in their natural environment and express physiological levels of nuclear factors required for induction. We recently found that hPCIS incubated for 48 h retained intact morphology, ATP content, and ABCB1 activity. We also confirmed that rifampicin (30 µM)...

GENOTOXICITY/MUTAGENICITY TESTING OF SELECTED PRESERVATIVESMeeting abstracts

Jan Chrz, Danuše Očadlíková, Lukáš Malina, Lada Svobodová, Kristina Kejlová, Hana Kolářová, Alena Vlková

MMSL 2022, 91(88):37  

Three preservatives  used as ingredients in cosmetics and other consumer products (triclosan , triclocarban and resorcinol) were evaluated for their genotoxic/mutagenic potential by means of a set of in vitro alternative methods, namely Ames Test (MPF Test, Xenometrix, OECD TG 471) with strains TA 98, TA 100, TA 1535 and TA 1537, Comet assay on HaCat cell line (non-tumor human keratinocytes) and Mammalian chromosome aberration test (OECD TG 473) using human peripheral lymphocytes. In the chromosome aberration test all three chemicals were positive in the highest tested concentrations. Similarly, in the Comet assay  the percentage of DNA in tail...

INTERNATIONAL TRAIN-SAFEMD PROJECT: COLLABORATION TOWARDS IMPROVED SAFETY ASSESSMENT OF MEDICAL DEVICESMeeting abstracts

Helena Kanďárová, Dagmar Jírová, Winfried Neuhaus, Kristína Kejlová, Peter Pôbiš, Markéta Dvořáková, Ana Spilak, Markéta Dvořáková, Lada Svobodová, Alena Moulisová

MMSL 2022, 91(88):38  

Medical devices (MDs) have an irreplaceable role in modern healthcare. The term 'medical device' covers a broad spectrum of products that are crucial in diagnosis and treatment, disease prevention and improving the quality of life of people suffering from disabilities or injuries. MDs used in the oral cavity are usually those helping in the treatment of aphthae or canker sores irritations and lesions of the oral mucosa by forming a barrier that adheres to the oral mucosa and promotes healing. Dental materials and dental prosthetic devices are also an important group of MDs with apparent contact with oral mucosa.Most of the MDs bio-compatibility...

DISRUPTION OF THE ARYL HYDROCARBON RECEPTOR (AHR) SIGNALING ALTERS FUNCTIONS AND PRODUCTION OF SURFACTANT IN A HUMAN MODEL OF ALVEOLAR TYPE II CELLSMeeting abstracts

Karasová M., Vázquez-Gómez G., Pelková V., Kotasová H., Hampl A., Slavík J., Machala M., Vondráček J.

MMSL 2022, 91(88):39  

The aryl hydrocarbon receptor (AhR) is a well-known cellular sensor of xenobiotics and major transcription regulator of xenobiotics-metabolizing enzymes. Recent studies have indicated that AhR is also important for physiological immunological functions of barrier organs, such as skin, gut, and lung. Nevertheless, its functions in epithelial cells of barrier organs are far less explored. Alveolar epithelial type II cells (ATII), also known as type II pneumocytes, are important regulators of functions of alveolar epithelium, which contribute to its regeneration, and production of surfactant. Surfactant lipids and proteins, which cover alveolar epithelium,...

MEMANTINE AND ITS COMBINATION WITH ACETYLCHOLINESTERASE INHIBITORS IN PHARMACOLOGICAL PRETREATMENT OF SOMAN POISONING IN MICEMeeting abstracts

Jiri Kassa, Jana Zdarova Karasova

MMSL 2022, 91(88):40  

The efficacy of prophylactic use of memantine alone or in combination with clinically used reversible acetylcholinesterase inhibitors (pyridostigmine, donepezil, or rivastigmine) against soman toxicity and their influence on post-exposure therapy consisting of atropine and HI-6 was studied. The effectiveness was assessed by comparison of LD₅₀ values over 24 h after soman poisoning. Pyridostigmine failed to decrease the acute toxicity of soman. But memantine, donepezil and rivastigmine reduced the acute toxicity of soman, with donepezil showing the best efficacy. Combination of memantine with pyridostigmine or one of the centrally-acting...

IN VITRO  CYTOTOXICITY EVALUATION OF SELECTED MATERIALS FOR WOUND DRESSING APPLICATIONMeeting abstracts

Tereza Kauerová, Peter Kollár, Pavel Suchý

MMSL 2022, 91(88):41  

Every medical device that is in contact with human body must be subjected to series of biological tests during the risk assessment process. Cytotoxicity testing belongs to the group of endpoints for biological evaluation of medical devices and its whole process is defined in ISO 10993-5 “Biological evaluation of medical devices – Part 5: Tests for in vitro cytotoxicity”. In a short time, it provides an initial information about toxicity, which serves as a good indicator of general toxic properties and thus it can reduce the number of in vivo models required for subsequent toxicity analyzes. There are different approaches...

THE EFFECT OF POTENTIAL CARCINOGEN HARMAN ON SELECTED CYTOCHROME P450 ENZYMES IN RATSMeeting abstracts

Eva Klásková, Markéta Strakošová, Jan Juřica, Ondřej Zendulka

MMSL 2022, 91(88):42  

Harman is a heterocyclic aromatic amine discovered in coffee, cigarette smoke, roasted meat, or fish (1). However, carcinogenic properties of harmane were proved - partly explained by its interaction via the AhR receptor and induction of CYP1A1 (2). Cytochrome P450 (CYP) enzymes are responsible for the metabolism of 75 % of drugs used in clinical practice (3). Our study aimed to determine the effects of harman on the most important CYP variants in a preclinical experiment.Harman was administered to Wistar Albino rats intragastrically at the doses of 25, 40, and 64 mg/kg/day for 8 days (control group - 66% propylene-glycol). Microsomes were prepared...

NOVEL MODIFIED PRALIDOXIME DERIVATES AS POTENTIAL REACTIVATORS OF ORGANOPHOSPHATE-INHIBITED CHOLINESTERASESMeeting abstracts

Karolina Knittelova, David Malinak, Rudolf Andrys, Kamil Musilek

MMSL 2022, 91(88):43  

Acetylcholinesterase (AChE) oxime reactivators are used as antidotes to organophosphate (OP) poisoning, while butyrylcholinesterase (BChE) reactivators are suitable for pseudocatalytic uptake of OP. OP acts as irreversible inhibitors of AChE. Due to the inhibition of AChE OPs cause impairment of cholinergic functions, which can lead to the death of the organism (1). The modification of the already known structure of pralidoxime aims primarily at overcoming the problems associated with physicochemical properties. The disadvantage of quaternary pyridinium oximes, which have a permanently positive charge, is poor penetration across the blood-brain barrier...

SYNTHESIS AND IN VITRO EVALUATION OF NON-SYMMETRICAL MONOQUATERNARY AMMONIUM SALTS AS POTENTIAL REACTIVATORS OF INHIBITED CHOLINESTERASESMeeting abstracts

Zuzana Kohoutova, David Malinak, Tereza Hofmanova, Rudolf Andrys, Lukas Prchal, Jana Svobodova, Kamil Musilek

MMSL 2022, 91(88):44  

Organophosphorous compounds (OPs) such as nerve agents or pesticides are irreversible inhibitors of cholinesterases, namely Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE), causing cholinergic crisis (1). While inhibition of AChE can be lethal, inhibition of BChE has no adverse effects. Therefore, BChE can be used for scavenging OPs before it reaches AChE in CNS. BChE itself has no catalytic activity, but by joint administration of BChE and reactivator we can establish pseudo-catalytic bioscavenger (2). Reactivators cleave the OP moiety from the enzyme by making a covalent bond with it. Reactivators of AChE are already widely used (eg....

PISTACIA LENTISCUS – CYTOTOXICITY AND ANTI-INFLAMMATORY ACTIVITYMeeting abstracts

Věra Králová, Barbora Szotáková, Thi Hoang Huong Bui, Marie Elstnerová, Egle Milia

MMSL 2022, 91(88):45  

Pistacia lentiscus L. (PLL) is a wild-growing shrub from the Anacardiaceae family that occurs naturally in the Mediterranean. It has been used in traditional medicine for its many effects since the days of ancient Greece (1). PLL plant and processed products have been largely employed as oral antiseptic, anti-inflammatory, analgesic, and healing agents (2). Today, the scientific interest in these edible and not-edible parts of PLL is wide-spreading, as some studies underlined the potential benefit against inflammation and infections (3). The aim of our work is to find out more details about biological activity of essential oil and aqueous extract...

NEW ADVANCED BIOPOLYMER MATERIALS IN THE TREATMENT OF ACUTE SKIN WOUNDSMeeting abstracts

Alžběta Kružicová, Marta Chalupová, Jarmila Klusáková, Gabriela Kuzmínová, Tomáš Parák, Tomáš Sopuch, Pavel Suchý

MMSL 2022, 91(88):46  

A cascade of events, including platelet aggregation, cytokine release, inflammation, fibroblast proliferation, angiogenesis and re-epithelialization, occurs in a healing wound. These processes are necessary for the proper course of healing, scar formation and remodeling. To accelerate healing of skin wounds, novel advanced, porcine and equine collagen/tencel based dressings, were fabricated. Collagen plays a pivotal role in each phase of healing due to its chemotactic role. It attracts different types of cells such as fibroblasts and keratinocytes to the wound. This supports angiogenesis and re-epithelialization. To monitor biological efficacy,...

REACTIVATION OF ACETYLCHOLINESTERASE INHIBITED BY NOVICHOK AGENTS – A COMPUTATIONAL STUDYMeeting abstracts

Tomas Kucera, Zbynek Vecera, Jakub Fibigar

MMSL 2022, 91(88):47  

Novichoks are a set of militarily abused substances from the group of nerve agents. The mechanism of their action is the covalent binding to Ser203 of acetylcholinesterase and inhibition of acetylcholine degradation. Any in vitro or in vivo experimental studies of novice-inhibited acetylcholinesterase reactivation have not been published yet (1). However, the possibilities of reactivation can also be investigated computationally. For this study, we used the methods of molecular docking in combination with molecular dynamics.We hypothesized that reactivation of novichok-inhibited acetylcholinesterase is not possible for steric reasons....

CHOLINESTERASES INHIBITED BY NOVICHOK AGENTS – IN SILICO  STUDY OF REACTIVATION POSSIBILITIESMeeting abstracts

Tomas Kucera, Zbynek Vecera

MMSL 2022, 91(88):48  

Both molecular docking and molecular dynamics was used to visualise the active or blocked site of AChE, and to determine affinity values in silico modelling. Selection of 60 ligands (including commercially available reactivators, e.g. trimedoxime, asoxime) from peer-reviewed articles (2) were docked into into proximity of AChE-A230 complex bond using software AutoDock Vina (v. 1.1.2). The most promising 32 ligands docked in AChE were evaluated by molecular dynamics (GROMACS 2020.4 software).Evaluation of specified simulations using Visual Molecular Dynamics (VMD) software has shown that the closest distance between the oxime group of the...

SYNTHESIS OF PYRIMIDINE DERIVATIVES WITH ANTITUBERCULAR ACTIVITYMeeting abstracts

Martin Kufa, Vladimir Finger, Jan Korabecny, Jaroslav Roh

MMSL 2022, 91(88):49  

Tuberculosis (TB) is a transmissible infectious disease caused by the intracellular bacteria, Mycobacterium tuberculosis (MtB), (1) which is currently one of the top 10 leading causes of death in low and middle-income countries (2). During 2020, 5.8 million patients were diagnosed with TB, 1.5 million of them died. In that year, 150 thousand patients were infected with drug-resistant TB strain.1 M. tuberculosis can quickly develop resistance against anti-TB regimens, and if not cured adequately, it can evolve into MDR-TB (multidrug resistant TB) and XDR-TB (extensive-drug resistant TB) (1). Therefore, there is a critical need to develop...

EFFECTS OF CARVEDILOL ON BILE ACID HOMEOSTASIS IN MICE WITH NON-ALCOHOL STEATOHEPATITISMeeting abstracts

Hana Lastuvkova, Fatemeh Alaei Faradonbeh, Jolana Schreiberova, Milos Hroch, Hana Faistova, Jaroslav Mokry, Radomir Hyspler, Alzbeta Stefela, Petr Pavek, Stanislav Micuda

MMSL 2022, 91(88):50  

Bile acids (BAs) play a significant regulatory role in the pathophysiology of non-alcoholic steatohepatitis (NASH). The present study evaluates the modulation of BAs homeostasis by carvedilol, a nonselective blocker beta adrenoreceptor that is routinely used to treat cardiovascular complications accompanying NASH. NASH was induced in mice by a continuous 24-week high-fat diet (HFD) with glucose/fructose in drinking water. At week 21, individual groups of animals received carvedilol (10 mg/kg/day, p.o.) for three weeks. Biochemical and histological analysis has shown the effectiveness of a high-fat diet in inducing NASH. The spectrum of bile acid was...

ORGANOTYPIC AND MICROPHYSIOLOGICAL HUMAN TISSUE MODELS FOR TRANSLATIONAL TOXICOLOGY AND PHARMACOLOGYMeeting abstracts

Volker M. Lauschke

MMSL 2022, 91(88):51  

The number of successful drug development projects has been stagnant for decades despite major breakthroughs in chemistry, molecular biology and genomics. Unreliable translatability of preclinical in vitro and in vivo models has been identified as the cause of most failure. Organotypic and microphysiological culture of primary human cells has emerged as a set of promising tools for preclinical drug development to narrow this translation gap. In this talk I will provide an overview of our recent efforts in developing 3D human tissue cultures and microfluidic models for both efficacy and safety assessments. In addition, the talk will present...

PILOT STEPS TO DEVELOPMENT OF IN VITRO MODEL FOR STUDYING EFFECTS OF BISPHENOLS ON CARDIAC CELLSMeeting abstracts

Barbora Macakova, Anna Gardianova, Anna Jirkovska, Eduard Jirkovsky

MMSL 2022, 91(88):52  

Bisphenols (e.g. bisphenol A, BPA), are chemical compounds used in manufacturing of plastics and polluting the environment worldwide in nanomolar concentrations. Although the direct toxic effects of "environmentally relevant" concentrations are controversial, concerns are associated with their action as chemical disruptors because their structure is similar to estrogens. Several studies reported that BPA may cause adverse effects in humans and animals (1), including an interference with cardiac differentiation (2). Based on these concerns, BPA was gradually replaced during last decade with “next generation” bisphenols. However, little is...

ASSESSMENT OF PREVENTIVE USE OF ERGOTHIONEINE IN MODEL OF GESTATIONAL HYPOXIA IN RATSMeeting abstracts

Mojmír Mach, Michaela Piešová, Romana Koprdová, Alexandra Ballóová, Eduard Ujházy

MMSL 2022, 91(88):53  

Insufficient supply of oxygen to the fetus (prenatal hypoxia) is one of the impacts capable to disrupt the pre- and postnatal development of an affected individual. Even though antioxidant trials largely turned out to be negative, research is still ongoing to find an optimal antioxidant drug to prevent or treat pregnancy related complications. Focus has been on more selective antioxidants and has investigated intracellular sources of oxidative stress during pregnancy. Our study aimed to assess the use of L-Ergothioneine (ERG) as potential new therapy for prenatal hypoxia. ERG serves as an antioxidant and cellular protectant against various kinds of...

FLUORINATED AND CHLORINATED PYRIDINIUM OXIMES REACTIVATING CHOLINESTERASES INHIBITED BY NERVE AGENTSMeeting abstracts

David Malinak, Tamara Zorbaz, Tereza Hofmanova, Rudolf Andrys, Miroslav Psotka, Jana Svobodova, Lukas Prchal, Zrinka Kovarik, Kamil Musilek

MMSL 2022, 91(88):54  

Nerve agents are organophosphorus compounds (OPs) with very potent toxicity due to their irreversible inhibition of the essential enzymeacetylcholinesterase (AChE; EC 3.1.1.7), which is primarily important in the control of neurotransmission in synapses. The related enzyme butyrylcholinesterase (BChE; EC 3.1.1.8) is inhibited by OPs aswell. Compounds with an oxime group act as reactivatorsof the inhibited AChE by the nucleophilic displacement of OP moiety from the enzyme’s catalytic serine and are used as a pharmacological treatment after OP poisoning. However, restoration of the AChE activity is directly related to the oxime structure and standard...

CHEMICAL WEAPONS FROM THE PERSPECTIVE OF INTERNATIONAL AND NATIONAL LAWMeeting abstracts

Ivan Mašek, Otakar Jiri Mika, Jaroslav Padrnos

MMSL 2022, 91(88):55  

The history of the use of toxic substances goes back to the distant prehistory of mankind. Over time, man has acquired and perfected the knowledge gained in his life and gradually passed it on from generation to generation. The authors recall the basic milestones before and during the emergence of chemical weapons, focusing on the widespread use of chemical weapons during the First World War. However, other armed conflicts are also mentioned, when chemical weapons were used as an important means of warfare (for example, Vietnam War, the Iraq-Iran War, etc.).Selected specific cases of misuse of chemical warfare agents for terrorist purposes are...

EFFECT OF PHARMACEUTICALY DRUGS METOPROLOL, ENALAPRIL AND METFORMIN ON EARLY LIFE STAGES OF ZEBRAFISH (DANIO RERIO)Meeting abstracts

Denisa Medkova, Pavla Lakdawala, Aneta Hollerova, Jana Blahova, Eva Postulkova, Jan Mares, Zdenka Svobodova

MMSL 2022, 91(88):56  

The level of contamination of the aquatic environment with residues of drugs as metoprolol, enalapril and metformin is constantly increasing. One of the reasons is the increasing prescribes and uses of these drugs, second is imperfect purification in wastewater treatment plants. Since the pharmaceuticals are entering water bodies continuously, they represent a potential risk for non-target aquatic biota. In our study, the toxicity of metformin, metoprolol and enalapril on zebrafish (Danio rerio) embryos in five different concentrations was tested. The acute toxicity test was performed according to OECD Guideline No. 236: Fish Embryo Acute Toxicity...

2-PROPARGAYLAMINO-NAPHTHOQUINONE DERIVATIVES AS MULTIPOTENT AGENTS FOR THE TREATMENT OF ALZHEIMER’S DISEASEMeeting abstracts

Eva Mezeiova, Jan Konecny, Jana Janockova, Rudolf Andrys, Ondrej Soukup, Tereza Kobrlova, Lubica Muckova, Jaroslav Pejchal, Miriama Simunkova, Jiri Handl, Petra Micankova, Jan Capek, Tomas Rousar, Martina Hrabinova, Eugenie Nepovimova, Jose Luis Marco-Contelles, Marian Valko, Jan Korabecny

MMSL 2022, 91(88):57  

Alzheimer’s disease (AD) is a progressive brain disorder with characteristic symptoms and several pathological hallmarks. The concept of “one drug, one target” has not generated any new drugs since 2004. The new era of drug development in the field of AD builds upon rationally designed multi-target directed ligands that can better address the complexity of AD (1). Herewith, we designed ten novel derivatives of 2-propargylamino-naphthoquinone. The biological evaluation of these compounds includes inhibition of monoamine oxidase A/B, inhibition of amyloid-beta aggregation, radical-scavenging, and metal-chelating properties. Some of...

SELECTED AND SERIOUS BELOW-LIMIT SOURCES OF CHEMICAL RISK IN THE CZECH REPUBLICMeeting abstracts

Otakar Jiri Mika

MMSL 2022, 91(88):58  

The paper deals with industrial chemical safety with a focus on major chemical accidents, hazardous chemicals and mixtures with emphasis on the dangers of selected sub-limit sources of risk. Currently, the two main laws in force, the Major Accident Prevention Act of 2015 (1), or the so-called "Chemicals Act" or the Chemicals and Mixtures Act of 2011 (2), have failed to address the serious safety issues of the so-called "Sub-threshold sources of risk" consisting of the low masses of hazardous chemicals.Until 2017, there was no clearly defined professional methodology, procedure or other tool to assess risk assessment of sources with hazardous...

NATURAL PHENOLIC COMPOUNDS AND BIOLOGICAL TRACE METALS: DOUBLE-EDGED SWORDMeeting abstracts

Přemysl Mladěnka

MMSL 2022, 91(88):59  

Many natural (poly)phenolic compounds including flavonoids are able to chelate biological trace metals such as iron, copper and cobalt. On the other hand, they are also frequently reducing these metals to lower oxidation states. Although this later reduction process is commonly understood as an antioxidant effect, it might be also associated with recovery of the catalyst in the known metal-catalyzed Fenton chemistry and can hence paradoxically lead to a tissue damage (pro-oxidation). For this reason, the final biological outcome ensuing from (poly)phenol-metal interaction varies from compound to compound depending on the individual differences in chelation...

NERVE AGENT INHIBITED CHOLINESTERASES CAN BE EFFICIENTLY REACTIVATED BY OXIMES WITH ENHANCED NUCLEOPHILICITYMeeting abstracts

Kamil Musilek, David Malinak, Tamara Zorbaz, Rudolf Andrys, Zuzana Kohoutova, Karolina Knittelova, Adam Skarka, Monika Schmidt, Zrinka Kovarik

MMSL 2022, 91(88):60  

Organophosphorus compounds (e.g. nerve agents - sarin, VX or tabun) cause deleterious intoxications via inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) leading to cholinergic crisis or even death of intoxicated person. Their causal treatment is managed by oxime reactivators (e.g. pralidoxime, obidoxime, asoxime), which are primarily restoring function of AChE via nucleophilic oximates and thus safe a life.Recently, we have proved that nucleophilicity of oxime reactivators may be improved by using other substituents attached to the close proximity of the oxime moiety. Such modifications are leading to the increased formation...

TOTAL MERCURY IN GREATER MOUSE-EARED BATS (MYOTIS MYOTIS) FROM THE LOCALITY WITH COAL MINING HISTORYMeeting abstracts

Kamila Novotna Kruzikova, Jiri Pikula, Petr Linhart, Hana Bandouchova, Jana Sedlackova, Zdenka Svobodova

MMSL 2022, 91(88):61  

The mercury is a persistent and whidespread heavy metal with neurotic effects in wildlife. To determine the overall mercury exposure in the locality Zastávka u Brna (Czech Republic), total of 71 great mouse-eared bats (Myotis myotis) building demolition casualties (23 male and 48 female) were examined. Bats were classified as juvenile or adult. The 71 samples of fur, muscle and wing membrane were collected for analysis to determine total mercury concentrations (THg). The THg was determined by cold vapour atomic absorption spectrometry using AMA 254 analyzer (Altec Ltd., Dvur Kralove nad Labem, Czech Republic) in the fresh weight. The THg measured...

IN VITRO MODEL OF NON-ALCOHOLIC FATTY LIVER DISEASE: THE EFFECT OF XANTHOHUMOLMeeting abstracts

Ehiofomwan Ameze Omwanghe, Michaela Šadibolová, Gabriela Svobodová, Martin Ambrož, Iva Boušová

MMSL 2022, 91(88):62  

Non-alcoholic fatty liver disease (NAFLD) is a pathological state characterized by the excessive accumulation of triglycerides in hepatocytes without alcohol consumption. NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which can further progress to cirrhosis and hepatocellular carcinoma (1). Xanthohumol (XN), a hop-derived prenylflavonoid, has been reported to ameliorate steatosis, inflammation, and fibrosis in murine NAFLD models (2). This study aimed to investigate the effect of XN on the expression of antioxidant enzymes in an in vitro model of NAFLD. For this purpose, fat accumulation was induced in murine...

EFFECTS OF BENZO[K]FLUORANTHENE ON PROTEOSYNTHESIS AND SELECTED METABOLIC GENES IN A MODEL OF IMMORTALIZED HUMAN HEPATOCYTESMeeting abstracts

Jiří Petráš, Miroslav Machala, Jan Vondráček

MMSL 2022, 91(88):63  

Polyaromatic hydrocarbons (PAHs) are a diverse group of environmental and dietary contaminants. PAHs are primarily metabolized through the aryl hydrocarbon receptor (AhR)-regulated enzymatic pathway. Both parent PAHs and their metabolites may exert various types of toxicity in target cells and tissues. In addition to their well-known genotoxic (and carcinogenic) effects, PAHs may alter numerous additional cellular events, including cell metabolism. In this project, we study whether strong AhR ligand benzo[k]fluoranthene (BkF) can modulate genes associated with glucose and lipid metabolism, as well as proteosynthesis, which is essential metabolic process...

IN VITRO  BIOCOMPATIBILITY TESTING OF MEDICAL DEVICES IN VITRO: CHALLENGES OF SAMPLE PREPARATION ACCORDING TO THE ISO 10993-12Meeting abstracts

Peter Pobiš, Júlia Kubalcová, Helena Kanďárová

MMSL 2022, 91(88):64  

The ISO standard 10993 for medical device testing was accepted over three decades ago. During that period, ISO standard was changing and adapted based on the growing knowledge on adverse effects and regulatory needs. The term, medical devices, includes various products that are used in medicine, but their terapeutic effect is not acchieved by pharmacological, immunological or metabolic means. These products have different mechanical, physical and chemical properties. The procedures described in the ISO 10993 cover testing of raw materials as well as final products. However, composition of  medical devices can be quite complex, and it may sometimes...

IN VITRO EVALUATION OF BODIPY LABELED BISQUATERNARY AMONIUM SALTS USED AS REACTIVATORS OF INHIBITED ACETYLCHOLINESTERASEMeeting abstracts

Eliska Prchalova, David Malinak, Jana Svobodova, Lukas Fresser, Rudolf Andrys, Zbynek Heger, Kamil Musilek

MMSL 2022, 91(88):65  

Oxime reactivators are causal antidotes commonly used against organophosphate (OP) poisoning. Although OPs are utilized in agriculture as pesticides, they can be misused by terroristic groups as nerve agents (NA). These compounds are fast acting inhibitors of human acetylcholinesterase (AChE) causing cholinergic crisis ultimately leading to death by respiratory failure. Treatment of OP intoxication consists of immediate administration of symptomatic drugs, namely, atropine and diazepam and antidotes in form of oxime reactivators of AChE. Undoubtedly commercially used reactivators are the best countermeasure for OP intoxications so far, however...

SYNTHESIS OF STATTIC-CARBOXAMIDES AND EVALUATION OF ITS BIOLOGICAL ACTIVITY AS STAT3 INHIBITORSMeeting abstracts

Miroslav Psotka, David Malinak, Rudolf Andrys, Jana Svobodova, Kamil Musilek, Milan Reinis

MMSL 2022, 91(88):66  

Signal transducer and activator of transcription-3 (STAT3) is the most studied member from seven latent cytoplasmatic transcription factors (STATs 1-4, 5a, 5b and 6) that are closely associated with the occurrence of many types of cancer (breast, leukemia, lung, lymphoma, ovarian and prostate). STAT3 contains four functional domains, from which the Src homology 2 domain (SH2 domain) is the major target for inhibition of these proteins. Inhibition results in STAT3 tyrosine 705 (Y705) phosphorylation, dimerization, nuclear transport, DNA binding and transcription induction. The benzo[b]thiophene 1,1-dioxide (BTP) as a pharmacophore is part of many STAT3...

IN VITRO MODEL EXPRESSING ACETYLCHOLINESTERASE FOR EVALUATION OF NEUROTOXICITY AND NEUROPROTECTIONMeeting abstracts

Pulkrabkova L., Muckova L., Hrabinova M., Kobrlova T., Janousek J., Soukup O.

MMSL 2022, 91(88):67  

Neurotoxicity is commonly associated not only with neurodegenerative damage but also with organophosphate intoxication. Neuronal death may be associated with acute and life-threatening symptoms and subsequent long-term secondary disorders. This study focuses on the development and validation of a cellular model of mature human neurons. A model was obtained by differentiating the neuroblastoma cell line SH-SY5Y. In vitro cell model is suitable for studying neurotoxicity and its potential countermeasures. The protocol involved stimulation of the cell line with retinoic acid and brain-derived neurotrophic factor for 9-12 days. Observation of morphological...

HETEROLOGOUS EXPRESSION OF SDR ENZYMES FROM H. CONTORTUSMeeting abstracts

Nikola Rychlá, Petra Matoušková, Lucie Raisová Stuchlíková

MMSL 2022, 91(88):68  

The aim of this project is heterologous expression of chosen carbonyl-reducing enzymes from Haemonchus contortus, a gastrointestinal nematode of small ruminants. Carbonyl-reducing enzymes (such as SDR and AKR) catalyze the first phase of xenobiotics biotransformation and thus participate in drug metabolism. Increased elimination leads to  decreased toxicity and reduced efficacy of drugs in Barber´s pole worm. One of the proven mechanisms of  deactivation of anthelmintics (e.g., flubendazole) is the reduction of the carbonyl group by these enzymes.In addition, the previous metabolism analysis has demonstrated a higher ability of...

THE SUBLETHAL EFFECTS OF SYNTHETIC PYRETHROID TAU-FLUVALINATE ON ADULT HONEYBEESMeeting abstracts

Lucia Sabová, Simona Koleničová, Rastislav Sabo

MMSL 2022, 91(88):69  

Nowadays, pyrethroids (e.g., flumethrin and tau-fluvalinate) are commonly used in apiculture as an active ingredient of several authorised veterinary medicinal products (acaricides) licensed worldwide. The beekeepers who regularly use synthetic acaricides throughout the year may potentially put the bee colonies at risk. Pyrethroids are frequently related to long half-life inside the hive matrices, which may adversely affect the health of bee colony. In this project we assessed potential harmful lethal and sublethal effects of synthetic acaricide tau-fluvalinate (tech.) on winter adult honeybees according to OECD 245 (2017). In vitro reared winter honeybees...

THE HEPATOTOXICITY OF HELENALIN IN DIFFERENTIATED HEPARG CELLSMeeting abstracts

Michaela Šadibolová, Gabriela Svobodová, Ehiofomwan Ameze Omwanghe, Juraj Lenčo, Iva Boušová

MMSL 2022, 91(88):70  

Helenalin (HEL) is a sesquiterpene lactone used as an antiphlogistic in European and Chinese folk medicine. Its characteristic anti-inflammatory activity is mediated by direct alkylation of Cys38 within the DNA binding domain of NF-κB subunit p65/RelA. In addition, HEL is a broad-spectrum active compound, featuring an antitumor, antibacterial, and antiprotozoal activity. Recently, a new interest in the biological and pharmacological activities of HEL or its synthetic analogs has been observed (1). HEL has been found to undergo oxidative as well as reductive biotransformation in human liver. In addition, HEL acted as a mechanism-based inhibitor...

ASSESSMENT OF IN VITRO NEUROXICITY OF SILVER NANOPARTICLES IN PC12 CELLSMeeting abstracts

Sona Scsukova, Martina Martincova, Alzbeta Bujnakova Mlynarcikova

MMSL 2022, 91(88):71  

Despite widespread use of metal nanoparticles (NPs) in diagnostic and therapeutic applications for neurodegenerative disorders, there is a lack of reliable neurotoxicological studies on the exact molecular mechanisms of NPs action on neuronal cells (1). The aim of the present study was to evaluate neurotoxic potential of silver NPs (AgNPs) of different sizes (10, 100 nm) in rat pheochromocytoma cells PC12. The cells were cultured in the presence of AgNPs (0.1–10 µg/ml) for different time periods (3–72 h) depending on the used analysis. Cell viability was assessed by detection of mitochondrial activity based on the MTT reduction and...

CAN THE ACCUMULATION OF NANOGRAPHENE IN CELLS CHANGE THEIR MOTILITY?Meeting abstracts

Ladislava Schröterová, Blanka Šestáková, Aleš Bezrouk, Dana Čížková, Emil Rudolf, Věra Králová

MMSL 2022, 91(88):72  

Graphene has been used increasingly in recent years in many fields for its unique physical, chemical and optical properties such as optical sensitivity, electronic and thermal conductivity. (1, 2). For this reason, it is important to verify its biocompatibility and the effect of graphene cell accumulation on metabolism, cell proliferation and motility. We tested a stable lung epithelial cell line A549 treated with chronic doses of nanographene platelets PlasmaChem GmbH (Berlin, Germany, product number PL-P-G750) in non-toxic concentrations of 5, 15 and 30 μg/ml graphene for 8 weeks. After this long-term cultivation the cells were analysed for...

PORCINE MYCOTOXIC NEPHROPATHY IN THE CZECH REPUBLIC - OCCURRENCE OF OCHRATOXIN A IN PIG KIDNEYS IN YEARS 2012-2021Meeting abstracts

Zuzana Široká, Petr Linhart, Alena Honzlová, Veronika Vlasáková, Zdeňka Svobodová, Martin Svoboda

MMSL 2022, 91(88):73  

Mycotoxic nephropathy of pigs is mainly associated with ochratoxin A exposure, so it is a chronic poisoning. Ochratoxin A is a mycotoxin produced by several species of fungi from the genera Aspergillus and Penicillium on a wide range of agricultural commodities used for feed production. The severity of the disease is determined by the amount of ochratoxin ingested and the duration of its action. Lower concentrations of ochratoxin A in the feed may not cause obvious clinical signs, but lead to findings during pathological-anatomical examination of the kidneys of slaughtered animals. In addition to nephrotoxicity, which can lead to kidney failure and...

COMPARISON OF TOPOISOMERASE 2 INHIBITORS DEXRAZOXANE AND XK469 FOR THE PREVENTION OF ANTHRACYCLINE CARDIOTOXICITYMeeting abstracts

Veronika Skalická, Jan Kubeš, Lenka Applová, Galina Karabanovich, Petra Brázdová, Olga Lenčová, Martin Štěrba, Jaroslav Roh, Tomáš Šimůnek, Anna Jirkovská

MMSL 2022, 91(88):74  

Despite its unprecedented efficacy against some cancers, anthracycline cardiotoxicity represents the main limitation of its clinical use. Its’ mechanisms are elusive, but quite recently TOP2B was addressed as a possible target in cardiomyocytes (1). This study introduces the putative TOP2B selective inhibitor XK469 (2) as a potential cardioprotective agent in the management of anthracycline cardiotoxicity. Its’ potential was compared with the cardioprotection of the only approved cardioprotective drug dexrazoxane (DEX, ICRF-187) (3). Initially, the selectivity of XK469 and the character of TOP2 inhibition were re-examined in vitro...

TARGETING TACRINE HEPATOTOXICITY ASSOCIATED WITH THE CYP BIOTRANSFORMATIONMeeting abstracts

Ondrej Soukup, Martin Novak, Lukas Prchal, Jan Korabecny, Martin Horak, Karel Vales

MMSL 2022, 91(88):75  

Current symptomatic pharmacotherapy for Alzheimer’s disease is primarily focused on acetylcholinesterase inhibitors and blocking of the NMDA receptor (N-methyl-D-aspartate). Tacrine, a molecule with both of the mechanisms of action, was withdrawn from the market in 2013 after 20 years of use due to the hepatotoxicity probably caused by its 7-hydroxytacrine metabolite. A rationale substitution of the tacrine molecule can potentially hinder the formation of a toxic species. The introduction of the methoxy or phenoxy group to position 7 led to 7-phenoxytacrine (7-PhO-THA) which we hypothesize to bypass the toxic metabolization via 7-OH tacrine and...

3R STRATEGIES IN REPRODUCTIVE TOXICOLOGY AND BIOMEDICINEMeeting abstracts

Iva Sovadinová, Eliška Sychrová, Ishita Virmani, Mahdia Bushra, Lola Bajard, Darshak Gadara, Zdeněk Spáčil, Pavel Babica

MMSL 2022, 91(88):76  

Reproductive health is challenged by contemporary lifestyles. Health issues such as menstrual problems, cancers, infertility, and sexual dysfunction have been rising (1-3). For example, nowadays, more than 20% of couples experience infertility problems (1). Recently, a growing piece of evidence supports an association between chemical exposure and reproductive disorders (2,3). Traditionally, animal models have been used to elucidate human reproductive health development, disorders, and pathologies, including mechanistic insight. Reproductive toxicity testing of chemicals for regulatory purposes also relies on them. Therefore, it is vital to address...

INTERACTION OF NEW POTENTIAL ANTIMICROBIAL COMPOUNDS WITH PORCINE MICROSOMAL CYP2DMeeting abstracts

Alena Špičáková, Zuzana Horáčková, Pavel Kopel, Eva Anzenbacherová, Pavel Anzenbacher

MMSL 2022, 91(88):77  

Antimicrobial drugs are chemical substances (of natural or synthetic origin) that suppress the growth of (or destroy) microorganisms (e. g. antibiotics act primarily against bacteria). Copper complexes ([Cu₂(pmdien)₂(H₂O)₂(μ-fu)](ClO₄)₂ – complex No. 5; [Cu₂(pmdien)₂(H₂O)₂(μ-dtdp)](ClO₄)₂ – complex No. 6), on which this study is focused, show antibacterial activity (1). As with every promising compound, these copper complexes were tested for their potential to inhibit activities of liver microsomal...

A PARADIGM SHIFT IN UNDERSTANDING THE MECHANISMS OF ANTHRACYCLINE CARDIOTOXICITY AND OPPORTUNITIES FOR EFFECTIVE PHARMACOLOGICAL CARDIOPROTECTIONMeeting abstracts

Martin Štěrba

MMSL 2022, 91(88):78  

Anthracycline (ANT) anticancer drugs (e.g., doxorubicin and daunorubicin) are known for their cardiotoxic effects which are associated with degenerative changes in cardiomyocytes, programmed and non-programmed cell death, pathological remodeling of the myocardium and cardiomyopathy development. Historically, the predominant hypothesis of ANT cardiotoxicity development emphasized redox cycling of ANT molecule in the heart with or without participation of free iron resulting to ROS production and direct oxidative damage to the heart. However, different antioxidants and selective biocompatible iron chelators largely failed in clinically relevant experimental...

FLUBENDAZOLE-INDUCED CHANGES IN THE EXPRESSION OF SDR GENES IN HAEMONCHUS CONTORTUSMeeting abstracts

Karolína Štěrbová, Petra Matoušková, Lenka Skálová

MMSL 2022, 91(88):79  

Drug-metabolizing enzymes represent the main defense system against xenobiotics in all organisms. Long-term exposure to drugs can lead to changes in the expression of specific enzymes and to development of drug resistance. The previous studies have shown that increased anthelmintics inactivation via increased expression of certain drug-metabolizing enzymes belongs to a significant mechanism of drug resistance in Haemonchus contortus.H. contortus, a gastrointestinal parasite of ruminants, has developed resistance to all used anthelmintics. As short-chain dehydrogenases/reductases (SDRs) catalyze the deactivation of carbonyl-containing...

TACRINE-SQUARAMIDE DERIVATIVES AS POTENT CHOLINESTERASE INHIBITORSMeeting abstracts

Barbora Svobodova, Eva Mezeiova, Yitian Zhou, Gabriel Herras Arribas, Ainoleena Turku, Tuuli Jurgenson, Souren Mkrtchian, Kristi Krebs, YiWang, Lili Milani, Gunnar Schulte, Stefano Gastaldello, Volker M. Lauschke, Jan Korabecny

MMSL 2022, 91(88):80  

Tacrine was the first drug to be approved for Alzheimer´s disease (AD) treatment, acting as a cholinesterase inhibitor. The neuropathological hallmarks of AD are amyloid-rich senile plaques, neurofibrillary tangles, and neuronal degeneration. Squaramides (SQ) are derivatives of squaric acid that are widely used in a variety fields of experties. Examples of small molecules with incorporated squaramide scaffold are Perzinfotel or Navarixin. Considering the relatively simple synthesis approach and other interesting properties (rigidity, aromatic character, H-bond formation) of squaramide motif, we developed 21 novel dimers amalgamating squaric acid with...

HIGH-FAT DIET INDUCES CHANGES IN ACTIVITY AND EXPRESSION OF DRUG-METABOLIZING ENZYMES IN MOUSE LIVERMeeting abstracts

Gabriela Svobodová, Michaela Šadibolová, Ehiofomwan Ameze Omwanghe, Martin Ambrož, Lenka Maletínská, Iva Boušová

MMSL 2022, 91(88):81  

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial, complex, and chronic liver disease with increasing worldwide prevalence. Metabolic syndrome and obesity are the main risk factors associated with NAFLD. High-fat diet causes an excessive fat accumulation in the liver referred to as simple steatosis, which can further progress to more severe stages of NAFLD including non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. As NAFLD has been reported to cause changes in the liver homeostasis and metabolism of xenobiotics (1), the objective of this study was to investigate NAFLD-induced changes in the expression...

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS – POTENTIAL RISK FOR NON-TARGET AQUATIC ORGANISMSMeeting abstracts

Zdeňka Svobodová, Jana Láníková, Martin Ferenčík, Martin Svoboda, Jana Blahová, Marie Skočovská

MMSL 2022, 91(88):82  

Non-steroidal anti-inflammatory drugs (NSAIDs) are drugs with analgesic, antipyretic and anti-inflammatory effects. They are widely used in human and veterinary medicine. The most used NSAIDs include ibuprofen, diclofenac, naproxen. Due to their excessive use surface water pollution occurs. A total of 65 samples of surface water from the Elbe river basin were taken during August 2018 when the weather was constant without any significant fluctuations. The analysis was performed by means of liquid chromatography with tandem mass spectrometry (LC-MS/MS). A statistically significant negative correlation between the river flow rate in the monitored locations...

MANGANESE(III) PORPHYRINS AS ANTI- AND PRO-OXIDANTS IN HIGH-MOLAR-MASS HYALURONAN OXIDATIVE DEGRADATIONMeeting abstracts

Katarína Valachová, Peter Rapta, Ladislav Šoltés

MMSL 2022, 91(88):83  

The solution of high-molar-mass hyaluronan (HA) was subjected to oxidative degradation by ascorbate and cupric ions in the absence and presence of one of three ortho isomeric Mn(III) porphyrins or para isomeric Mn(III) porphyrin. Of methods, rotational viscometry was used, by which time-dependent changes in the dynamic viscosity of the HA solutions were measured. The ortho isomers MnTE-2-PyP⁵⁺, MnTnBuOE-2-PyP⁵⁺ and MnTnHex-2-PyP⁵⁺ interact with ascorbate whereby producing H₂O₂, which subsequently reacts with Cu(I) to initiate the hydroxyl radical-induced HA degradation. In contrast, when examining...

ARYL HYDROCARBON RECEPTOR (AhR) LIMITS THE INFLAMMATORY IMPACT OF EXTRACT OF REFERENCE DIESEL EXHAUST PARTICLES IN HUMAN LUNG EPITHELIAL A549 CELLSMeeting abstracts

Gerardo Vázquez-Gómez, Martina Karasová, Zuzana Tylichová, Marketa Kabatková, Aleš Hampl, Jason Matthews, Jiří Neča, Miroslav Ciganek, Miroslav Machala, Jan Vondráček

MMSL 2022, 91(88):84  

The aryl hydrocarbon receptor (AhR) is well known for its detoxification/bioactivation role. However, it has been suggested to participate also in the control of inflammatory responses. Diesel exhaust particles (DEP) are known to induce inflammation in respiratory tract. Here, we used standard reference mixture of diesel exhaust particles (SRM1650b) in order to evaluate the functional role of the AhR (using wild-type and AhR-deficient A549 lung epithelial cells) in the control of inflammatory responses towards DEP-associated pollutants. We compared their effects with those of pro-inflammatory cytokines, such as IL-1β. We found that the induction...

UNCOVENTIONAL ENVIRONMENTAL TOXIC LIGANDS OF THE ARYL HYDROCARBON RECEPTOR (AhR)Meeting abstracts

Jan Vondráček, Miroslav Machala

MMSL 2022, 91(88):85  

Activation of the aryl hydrocarbon receptor (AhR) represents a key toxic event elicited by numerous persistent organic pollutants and other environmental contaminants, such as polycyclic aromatic hydrocarbons (PAHs). Ar present, unlike so-called priority PAHs, the AhR-mediated activities of numerous other PAHs, substituted (e.g. methylated or halogenated PAHs) remain poorly defined. Importantly, these contaminants are often neglected, when toxicities of complex mixtures of environmental polyaromatic pollutants are being evaluated. Our past work has revealed that such compounds can indeed contribute significantly to overall AhR-mediated toxicities of...

TOXICITY TESTING OF NEW POTENTIAL ANTHELMINTICS IN PARASITIC NEMATODE HAEMONCHUS CONTORTUS AND OVINE LIVERMeeting abstracts

Markéta Zajíčková, Linh Thuy Nguyen, Oliver Michel, Thomas Kurz, Lenka Skálová

MMSL 2022, 91(88):86  

Haemonchus contortus, a widely distributed parasitic nematode of ruminants, has become resistant to most anthelmintic classes. Therefore, there has been a major demand for new compounds effective against H. contortus and related nematodes. Previous phenotypic screening and further testing have revealed one compound, substituted benzamide BLK127, active against H. contortus larvae and adults (1,2). Based on these results, 13 derivatives of this compound were designed and synthetized. The aim of the present study was to assess the toxicity of these derivatives in H. contortus eggs and adults and their potential hepatotoxicity...

PROTECTIVE EFFECT OF NATURAL COMPOUNDS: A CURCUMIN STUDYMeeting abstracts

Terézia Zajičková, Katarína Adamčíková, Stanislav Kyzek, Ivana Ďurovcová, Andrea Ševčovičová, Eliška Gálová

MMSL 2022, 91(88):87  

Since cancer is one of the most common medical causes of death worldwide, its prevention remains the most promising strategy for reducing its incidence and mortality. The study of the potential protective effects of natural compounds, that could be used in health protection, is therefore very important. Plants represent a source of secondary metabolites possessing such properties and curcumin isolated from plant Curcuma longa L. with many beneficial biomedical effects is one of them.The objectives of our study were (I) to investigate the potential DNA-damaging/DNA-protective effects of curcumin using DNA topology assay; (II) to determine...

NOVEL GEMINI-TYPE OF QUATERNARY AMMONIUM COMPOUNDS WITH STRONG ANTIMICROBIAL EFFECTMeeting abstracts

Natalie Zivna, Michaela Hympanova, Hana Strakova, Lenka Pulkrabkova, Jan Marek

MMSL 2022, 91(88):88  

Since the discovery of penicillin, antibiotic use and misuse lead to the development of bacterial strains resistant to not only antibiotics, but to common disinfecting agents as well. Monomeric quaternary ammonium compounds (QACs) – common disinfecting agents – are already rendered inefficient due to the acquired resistance. The development of novel agents is now a major component in the fight against the spread of diseases. New designs should enhance the advantages of existing substances (high efficacy, low price), while embracing biodegradability, improved solubility and lower cytotoxicity.In recent years new, yet related class...

OXIDATIVE STATUS ASSESSMENT OF RATS' BRAIN INJURY FOLLOWING SUBACUTE EXPOSURE TO K-OXIMESMeeting abstracts

Jelena Dumanović, Jelica Grujić-Milanović, Zoran Milovanović, Ljiljana Amidžić, Nataša Vojinović, Lana Nežić, Petar Milosavljević, Eugenie Nepovimova, Kamil Kuča, Vesna Jaćević

MMSL 2022, 91(88):89-90  

In this study, it has been investigated the oxidative status and morphological alterations in the brain of Wistar rats induced by repeated application of low doses of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, K074, and K075. Each oxime (0.1 of LD50/kg im) was given 2 times per week for 4 weeks. The animals’ whole-body, organ weight, oxidative status, as well as microscopic examination of the brain, were done on day 35 of the study. Markers of oxidative stress, lipid peroxidation (malondialdehyde (MDA) and advanced oxidation protein products (AOPP)), as well as the activity of antioxidant enzymes (catalase...

GK-667 - A NEW PROMISING CARDIOPROTECTANT AGAINST CHRONIC ANTHRACYCLINE CARDIOTOXICITY IN VIVOMeeting abstracts

Petra Kollárová, Olga Lenčová, Galina Karabanovich, Jan Kubeš, Nela Váňová, Yvona Mazurová, Michaela Adamcová, Tomáš Šimůnek, Petra Štěrbová, Jaroslav Roh, Martin Štěrba

MMSL 2022, 91(88):91  

Anthracyclines (ANT) are very effective anticancer drugs, but they are feared for their cardiotoxicity. The only drug approved to counteract this severe side effect in clinical settings is a bisdioxopiperazine dexrazoxane (DEX). However, another bisdioxopiperazine agent ICRF-193 was recently shown to be more effective than DEX in vitro. Its poor water-solubility was solved by design of its prodrugs, from which GK-667 was selected for in vivo studies. The aim of this study was to examine cardioprotective effects of GK-667 on a rabbit model of chronic ANT cardiotoxicity in vivo. Cardiotoxicity was induced with daunorubicin (DAU;...

A PARADIGM SHIFT IN UNDERSTANDING THE MECHANISMS OF ANTHRACYCLINE CARDIOTOXICITY AND OPPORTUNITIES FOR EFFECTIVE PHARMACOLOGICAL CARDIOPROTECTIONMeeting abstracts

Martin Štěrba

MMSL 2022, 91(88):92  

Anthracycline (ANT) anticancer drugs (e.g., doxorubicin and daunorubicin) are known for their cardiotoxic effects which are associated with degenerative changes in cardiomyocytes, programmed and non-programmed cell death, pathological remodeling of the myocardium and cardiomyopathy development. Historically, the predominant hypothesis of ANT cardiotoxicity development emphasized redox cycling of ANT molecule in the heart with or without participation of free iron resulting to ROS production and direct oxidative damage to the heart. However, different antioxidants and selective biocompatible iron chelators largely failed in clinically relevant experimental...

ZANUBRUTINIB ACTS AS AN EFFECTIVE RESISTANCE MODULATOR BY INHIBITING ANTHRACYCLINE METABOLISM AND EFFLUXMeeting abstracts

Lucie Čermáková, Jakub Hofman, Vladimír Wsól

MMSL 2022, 91(88):93  

Anthracycline (ANT) resistance represents a significant challenge in cancer therapy. Besides other mechanisms, ANT resistance is mediated by the metabolic activity of carbonyl-reducing enzymes (CREs) and/or the efflux activity of ATP-binding cassette (ABC) transporters. CREs reduce ANTs to their corresponding less potent alcohol metabolites, while ABC transporters pump ANT drugs out of cancer cells decreasing their concentrations below cytotoxic level. Among CREs, AKR1C3 is of great importance because its overexpression has been detected in many hematological and solid malignancies, similar to some ABC transporters such as ABCB1, ABCG2, and ABCC1....

TOXICITY OF NANOFIBERS AND NANOPARTICLES OF THE SAME CHEMICAL COMPOSITIONMeeting abstracts

Jana Báčová, Luděk Hromádko, Tomáš Roušar, Jan M. Macak

MMSL 2022, 91(88):94  

In this presentation, the first comprehensive toxicity study of Al₂O₃, SiO₂, ZrO₂, TiO₂ and WO₃ nanofibers effects in cultured epithelial A549 cells will be presented. The nanofibers were produced by centrifugal spinning from suitable spinning solutions and have an average diameter in the sub-micrometer range. At first, we characterized the nanofibers for their morphological, compositional and structural properties. Then, we estimated the biological effects of nanofibers in pulmonary epithelial A549 cells comparing them with biological effects of Al₂O₃, SiO₂,...

ONE-DIMENSIONAL NANOMATERIALS AND THEIR (NON)TOXICITYMeeting abstracts

Jana Báčová, Luděk Hromádko, H. Sopha, Tomáš Roušar, Jan M. Macak

MMSL 2022, 91(88):95  

This presentation will introduce one-dimensional nanomaterials that we have been developing for various applications over past years. Two main types of materials will be discussed – nanofibers of inorganic oxides and nanotubes of TiO₂.In the first part, the first comprehensive toxicity study of Al₂O₃, SiO₂, ZrO₂, TiO₂ and WO₃ nanofibers effects in cultured epithelial A549 cells will be presented. The nanofibers were produced by centrifugal spinning from suitable spinning solutions and have an average diameter in the sub-micrometer range. At first, we characterized...