Projects

National

Účinky prírodných a syntetických zlúčenín pri oxidačnom poškodení biomakromolekúl. Pro- a antioxidačné mechanizmy.
Effects of natural and synthetic compounds on oxidative damage of biomacromolecules. Pro-oxidative and antioxidative mechanisms.
Program: VEGA
Project leader: RNDr. Valachová Katarína , PhD.
Duration: 1.1.2019 – 31.12.2022
ACE2-TXZF – Nové perspektívy v liečbe kardiovaskulárnych komplikácií spojených s COVID-19
New perspectives in the treatment of cardiovascular complications associated with COVID-19
Program: SRDA
Project leader: RNDr. Čačányiová Soňa, PhD.
Annotation: Coronavirus disease 2019 (COVID-19), linked to severe acute respiratory syndrome induced by coronavirus-2(SARS-CoV-2), was declared as a global pandemic. While respiratory failure is the major cause of mortality due toCOVID-19, the great number of patients exhibit cardiovascular disorders. Understanding the underlyingmechanisms of cardiovascular complications associated with COVID-19 is of the great importance to reach theeffective therapy and to reduce mortality due to COVID-19. In this project we will imitate the inhibition of ACE2-mediated signalling induced by SARS-Cov-2 using highly specific ACE2 inhibitor MLN-4760. In thispharmacological model of COVID-19 in spontaneously hypertensive rats (SHR) we intend to examine the extend ofMLN-4760-induced vascular damage as well as the mechanisms underlying the action of taxifoline and zofenapril,as perspective pharmacological tools for the treatment of cardiovascular complications associated with COVID-19.TX has been chosen as it was shown as promising drug-like substance inhibiting SARS-Cov-2 replication viainhibition of the main protease (Mpro). ZF is sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitorspontaneously releasing hydrogen sulfide (H2S). Both substances provide several additional cardioprotectiveeffects associated with elevated NO bioavailability and H2S release, respectively. These effects can improvefunction of the cardiovascular system via elevation of NO and H2S-mediated vasodilatation, inhibition oftrombogenesis and induction of antioxidant and antiinflamatory action.
Duration: 16.9.2020 – 31.12.2021
Molekulárno-farmakologické prístupy k inovatívnej terapii reumatoidnej artritídy hodnotenej v experimentálnych podmienkach in vivo a in vitro
Program: SRDA
Project leader: PharmDr. Bauerová Katarína, PhD., DrSc.
Duration: 1.7.2016 – 30.6.2020
Protektívne účinky prírodných a syntetických látok pred oxidačným poškodením vysokomolekulového hyalurónanu, izolovaných živočíšnych buniek a ich mitochondrií
Protective effects of natural and synthetic substances against oxidative damage of high-molar-mass hyaluronan, isolated mammal cells and their mitochondria
Program: VEGA
Project leader: RNDr. Valachová Katarína , PhD.
Annotation: Hyaluronan (HA) is a polysaccharide of molar mass several megaDaltons present in tissues of vertebrates. In inflammatory diseases the average molar mass of HA decreases by action of oxidants. A significant decrease of synovial fluid (SF) viscoelasticity was detected, thereby its lubricating properties are worsened. High-molar-mass HA solutions are relevantly used for in vitro studies of free radicals and oxidants performance and also for a study of protective effects of antioxidants/drugs in a role of prevention or chain-breaking degradation of HA macromolecules.Substances of synthetic origin such as antiinflammatory drugs, mitochondria targeted antioxidants and natural substances with demonstrated antioxidative effects against HA degradation will be tested as protectors of oxidative degradation of cell lines of fibroblasts NIH-3T3, B-HNF-1, VH10 and cell organels, especially mitochondria.
Duration: 1.1.2015 – 31.12.2018
Štúdium pôsobenia reaktívnych foriem kyslíka a dusíka na vysokomolekulový hyalurónan, synoviocyty a chondrocyty
Study of Actions of the Reactive Oxygen/Nitrogen Species on High-Molar-Mass Hyaluronan, Synoviocytes, and Chondrocytes
Program: VEGA
Project leader: Ing. Šoltés Ladislav, DrSc.
Annotation: 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, which will have significant antioxidant effect against HA degradation will be tested in relation to their protective effect against damage of joint elements.
Duration: 1.1.2011 – 31.12.2014
Degradácia hyaluronanu reaktívnymi zlúčeninami kyslíka: Kinetika reakcie a molekulové charakteristiky generovaných polymérových fragmentov
Hyaluronan degradation by reactive oxygen species: The reaction kinetics and molecular characteristics of generated polymer fragments
Program: VEGA
Project leader: Ing. Šoltés Ladislav, DrSc.
Annotation: Hyaluronan (HA) is a polysaccharidic constituent of numerous tissues in the vertebrate organisms. 1 ml of synovial fluid (SF) – an essential joint component – contains 2-3 mg HA, which molar mass reaches in healthy adults magnitude about several MDa. However, at the inflammatory joint disorders, this value 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 substance/probe for in vitro investigations of the “damaging” action of oxidants and/or for evaluation of the efficacy of various substances to act as antioxidants.The goals to attain are1. To establish experimental study protocols enabling proper evaluation of the changes in viscoelasticity of the HA solution caused by oxidant(s): the experimental study protocol put-in-work should provide exact evaluation/classification of (novel) low-molar-mass substances/drugs to function as inhibitors/scavengers of the HA degradation caused by oxidants – mainly, •OH radicals.To clarify chemical, biochemical, and molecular-biological aspects of the protective effects of (novel) drugs in terms of their antioxidative/radical scavenging properties in order to elaborate a suggestion of relevant strategy of the combined therapy (a so-called multi-bullet concept) of the oxidative stress associated diseases: The major disease of concern will be inflammation of the joints – its initial acute phase.
Duration: 1.1.2008 – 31.12.2010
POLOS – Molekulové mechanizmy pôsobenia nových liečiv ovplyvňujúcich oxidačný stres – významný etiopatogenetický faktor početných chorôb
Molecular mechanisms of new drugs influencing oxidative stress – important ethiopathogenetic factor of numerous diseases
Program: SRDA
Project leader: Prof. MUDr. Bauer Viktor, DrSc.
Annotation: The project is aimed at understanding the mechanism of action of compounds with antioxidative and antiradical properties in tissue inflammation, ischemia/reperfusion, trauma, and chronic hyperglycemia, studied at preclinical level. It is supposed that the drugs may be used in inhibition of tissue oxidative impairment in stroke, neurotrauma, late consequences of diabetes, rheumatoid arthritis, myocardial infarction, etc. The outcome of the targeted analysis will be the suggestion of strategies in therapy, only rarely used in contemporary medicine. New knowledge on pharmacology of compounds interfering with oxidative stress (OS) will contribute to their use in combined prevention and therapy („the multibulletted concept“) of diseases in which OS is participating. The project will contribute to broadening the array of suitable medicines by new drugs with satisfactorily understood mechanism of action and will provide the rationale of pharmacologic intervention based on reduction of OS in tissues.
Duration: 1.9.2006 – 31.10.2009