The Department of Cellular Pharmacology and Developmental Toxicology
Head of Department
RNDr. Michal Dubovický, PhD.
Developmental Toxicology and Pharmacology Unit
The broad area of research interest in our department involves studies to elucidate mechanisms of hypoxia during sensitive stages of development and involvement of drug during organogenesis and “fine tuning” of central nervous system. Using a variety of animal models of human diseases in conjunction with biochemical, histology and behavioral methods of analysis, we seek to determine the extent to which these early influences can change the quality of later life. Screening for new prospective psychoactive drugs is also one of the research focuses. The Department utilises a spectrum of standard toxicological and behavioral methods such as screening for developmental anomalies, neurodevelopmental analysis, imunohistochemical-based assessment, anxiety- and depression-like behaviour observations, cognition and social behaviour evaluation. The department disposes a modern equipment necessary for teratological and behavioural studies.
Cellular Pharmacology Unit
The laboratory is engaged in the study of mechanisms of receptor as well as non-receptor interactions between cationic amphiphilic drugs and isolated cells at cellular and molecular levels. Especially the effect of beta-adrenoceptor blocking and antihistamine drugs, stobadine and chloroquine on blood platelets, polymorphonuclear leukocytes and on their mutual interactions is studied. In the presence of drugs, alterations in functions of tested cells (aggregability, release reaction, free radical generation, myeloperoxidase and beta-glucuronidase release) as well as in some cellular regulatory mechanisms (calcium displacement and movement, arachidonic acid metabolism, histamine and serotonin liberation) are investigated. Pharmacological effects are correlated with the structure and physico-chemical properties of drugs studied.
Pharmacology of Excitable Tissues Unit
Analysis of the mechanisms responsible for altered smooth muscle activity and endothelial and epithelial function, elicited by detrimental action of reactive oxygen species produced during pathological stages (e.g. ischaemia/reperfusion, diabetes mellitus, hypertension, arthritis). By applying techniques of pharmacology and biochemistry, the modulatory action of some drugs with antioxidant and scavenging properties (e.g. pyridoindols, natural products, etc.) on the ROS-induced injury of smooth muscle functions is determined and characterised.
Cardiovascular pharmacology, cell signalling mechanisms in myocardial and vascular smooth muscle cells and in compromised myocardial tisues, use of animal experimental models.
Study of the action of compounds affecting a generation and/or the action of reactive oxygen species on central nervous tissue damaged due to oxidative stress. The main aim has been pharmacological protection of the nervous system against oxidative stress occurring in some acute and chronic neurological diseases. The problem is being analyzed on receptor, biochemical, cellular, tissue, and whole animal level.
Bioorganic Chemistry of Drugs Unit
Hyaluronan (HA) is a polysaccharidic constituent of numerous tissues in the vertebrate organisms. One ml of synovial fluid (SF) – an essential joint component – contains 2-3 mg HA, which molar mass reaches in healthy adults the magnitude of about several megaDaltons. However, at the inflammatory joint disorders, the mean molar mass of HA is significantly decreased. This decrease is accompanied by a pronounced decline of the HA solution viscoelasticity and loss of the lubricating properties of SF. Low resistance of HA against the action of oxidative species – free radicals, anions – stimulated our efforts to use this biopolymer as a relevant (endogenic) substance for in vitro investigations of the “damaging” action of oxidants and/or for evaluation of the efficacy of various compounds/drugs to act as scavenging antioxidants.The substances such as antiinflammatory drugs, thiol substances, endogenous substances, pyridoindole derivatives and nutritional supplements which will have significant antioxidant effect against HA degradation will be tested in relation to their protective effect against damage of joint elements.