Studies of effects of drugs in various experimental pathological state

Research Group of Molecular and Cellular Toxicology

The main topic of the Research Group of Molecular and Cellular Toxicology, led by prof. Tomáš Šimůnek, is cardiotoxicity of drugs and potential of pharmacological cardioprotection. In collaboration with various laboratories, this group has contributed to the characterization of the role of oxidative stress in some cardiovascular disorders and identification of aroylhydrazone (pro)chelators of iron as effective cardioprotectants. In the study of anthracycline aticancer drugs, the focus has shifted to the role of topoisomerase IIβ. We are engaged in multidisciplinary collaborative project aimed at research and development of novel analogs of the cardioprotective agent dexrazoxane (ICRF-187). In the laboratory, there are established protocols for isolation of primary cultures of ventricular cardiomyocytes as well as work with various lines of cancerous (solid and leukemic) and non-cancerous cells. We employ in vitro models for the study of molecular mechanisms of cardiotoxicity of anticancer drugs (both anthracycline as well as novel “targeted” therapies) and other toxic xenobiotics. Apart from the cardiotoxicity and cardioprotection, we investigate effects of drugs (and their combinations) on proliferation of cancer cells, where we are focused on the study of biological properties of new (aza)phtalocyanine photosenzitizers for the photodynamic therapy of tumors. Apart from the common cytotoxicity/proliferation assays, we use confocal microscopy (including the live cell imaging) and flow cytometry. We analyze the role of mitochondrial damage, formation of the reactive oxygen species, induction of apoptosis and autophagy, as well as the effects of the substances on cell cycle.

Research group of Cardiovascular and respiratory pharmacology and toxicology

The group of cardiovascular and respiratory pharmacology and toxicology aims at the research of physiological, pathological, pharmacological and toxicological aspects of the cardiorespiratory system. The main topics are currently:

  • monitoring of biological effects of phenolic compounds of both natural and synthetic origin in the form of parent compounds and their metabolites (flavonoids including flavonolignans and isoflavonoids, coumarins, phenolic acids)
  • the study of novel antiplatelet drugs
  • analysis of the impact of compounds on vascular smooth muscles in vitro
  • monitoring of the effects of compounds on the cardiovascular system in vivo (arterial blood pressure, heart function)
  • screening of novel iron, copper and zinc chelators
  • determination of basic pharmacokinetic parameters
  • the study of novel bronchodilators in vitro a in vivo
  • the study on stress induced senescence in the heart

Workgroup of biological and medical sciences

Workgroup of Biological and Medical Sciences lead by prof. PharmD. Petr Nachtigal, Ph.D. is consists of three subgroups focused on Pathology and Pharmacology of the Cardiovascular system, Clinical Physiology of Nutrition and Metabolism, and Microbiology Immunology.

The subgroup of pathology and pharmacology of cardiovascular system is focusing on the study of endothelial dysfunction, atherosclerosis, and liver metabolism in experimental in vitro and in vivo models. Our primary objective is the study of tissue and soluble endoglin (CD105, TGF-βRIII) and its related signaling in endothelial dysfunction and atherogenesis in a mouse model of atherosclerosis and nonalcoholic steatohepatitis (NASH) in vivo and in vitro in endothelial cells reviewed which was recently reviewed by Vicen et al. 2020. Moreover, we study the effects of various drugs (statins, Carotuximab) on tissue and soluble endoglin-related signaling both in vivo and in vitro. Our group cooperates with various partners, including prof. Carmelo Bernabeu, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain, Dr. Miguel Pericacho, University of Salamanca, Spain and prof. Chlopicki, Jagiellonian Centre for Experimental Therapeutics (JCET), Krakow, Poland

The subgroup of Clinical Physiology of Nutrition and Metabolism deals with the study of energy expenditure, bioimpedance spectrometric analysis of body composition and nutrition in women during pregnancy, childbirth, and lactation in collaboration with the Obstetric and Gynecological Clinic. In conjunction with the previous NutrGrav study, which brought the world's first predictive equation for resting energy expenditure (Hronek et al., 2009), demonstrated fat free mass as a predictor of resting energy need (Hronek et al., 2011) and determined the individual nutritive intake during pregnancy (Hronek et al., 2013). The second clinical study in collaboration with the Surgical Clinic - ICU focuses on the study of nutritional support due to the energy requirements and nutritional substrates utilization in polytraumatized patients, which clarified the specifics of the oxidation of the nutritional substrate whose application contributes to decreasing of morbidity and mortality (Patková et al., 2018).

The subgroup of Microbiology and Immunology is engaged in the study of antimicrobial activity of newly synthesized compounds (cooperation with chemical departments) or prepared derivatives of natural compounds (cooperation with the Department of Pharmacognosy). Basic screening includes the determination of the antibacterial, antimycobacterial, and antifungal efficacy of these compounds. In case of interesting activity, advanced methods are available, allowing to preview other properties of investigated substances. For example, determination of activity against biofilm-forming microorganisms, determination of the mechanism of action at macromolecular level or in vivo study including invertebrate model of Galleria mellonella. Another aim is to study the biofilms from the point of view of their formation, quantification, and possible eradication possibilities. Biofilms are nowadays one of the main problems accompanying antimicrobial resistance. (Konecna et al., 2021, Diepoltova et al., 2021). Finally, this subgroup is engaged in the study of infections caused by yeast of the genus Candida, focusing on vulvovaginal candidiasis. An integral part of this study is monitoring the host-pathogen interactions regarding the virulent potential of these microorganisms (Konecna et al., 2019). The whole subgroup cooperates closely with the Institute of Clinical Microbiology, Faculty Hospital in Hradec Kralove.

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