Ivo Juránek | Slovak Academy of Sciences (original) (raw)
Papers by Ivo Juránek
General physiology and biophysics, 2005
For a decade or two, the hypothesis of causality of various disorders by reactive oxygen species ... more For a decade or two, the hypothesis of causality of various disorders by reactive oxygen species (ROS), due to their potentially harmful effect towards cellular constituents, is one of the most frequently cited in biomedical sciences. In fact, the ROS-mediated alterations of biomacromolecules are considered to be essential events in the etiopathogenesis of those diseases where involvement of ROS has been indicated. ROS easily react in vitro with most biological molecules, causing their degradation and destruction. This may implicitly suggest that, when excessively produced in vivo, ROS are deleterious to integral components of the cell and cause their dysfunctions. Some experimental data indicate that ROS-mediated lipid peroxidation, protein oxidation and oxidative alterations to nucleic acids are crucial events of unfavorable actions of ROS. Yet the most convincing evidence, i.e. unambiguous inhibition of tissue injury by pretreatment with antioxidants, has not been provided. On th...
Central European journal of public health, 2004
The present study was designed to investigate mechanisms of adenosine (ADO)-mediated prolongation... more The present study was designed to investigate mechanisms of adenosine (ADO)-mediated prolongation of conductivity through the atrioventricular (AV) node during myocardial ischemia. Using the Langendorff preparation of the guinea pig heart, we tested the hypothesis that extracellular potassium concentration elevated due to ischemia could augment ADO effect. Exposure of the heart preparation to either stop-flow or hypoxic Krebs-Henseleit solution (KH) inhibited AV node conductivity observed as an increase in SH interval, and finally resulted in AV block. Superficial potassium concentration ([K+]s), recorded simultaneously increased in response to each stop-flow or hypoxia. Application of 0.1 mM BaCl2 markedly increased the SH interval, yet it did neither protect the heart from hypoxia-evoked AV block nor did it prevent hypoxia-induced [K+]s elevation. Neither did perfusion of the myocardium with modified KH containing 8 mM K+ affect the hypoxic AV block and [K+]s increase. The hypoxic...
Die Pharmazie, 1995
The effect of selected carbanilates on the rat gastric mucus was tested after oral administration... more The effect of selected carbanilates on the rat gastric mucus was tested after oral administration. The compounds K 1905 and K 2002 were found to increase gastric mucus content in nonstressed rats while compound P 2 was ineffective. The activity of K 1905 was comparable with that of the parent drug trapencaine. Cold-restraint stress decreased the gastric mucus content and induced haemorrhagic erosions in the glandular stomach. With the exception of compound P 2 pretreatment with carbanilates dose-dependently diminished the extent of stress-induced gastric damage and prevented the depletion of mucus after stress. The results indicate that pentyloxy-substitution in the meta and in the para position on the benzene ring of the parent structure (K 1905 and K 2002, respectively) seems to be more suitable for mucus enhancing activity than alkyloxy-substitution on the para position (P 2). The observed increased mucus secretion might be partly responsible for the gastroprotective action of th...
Acta Veterinaria Brno, 2014
The study concentrated on behavioral and magnetic resonance imaging (MRI) characteristics in a po... more The study concentrated on behavioral and magnetic resonance imaging (MRI) characteristics in a porcine spinal cord injury model. Six adult minipigs weighing 32-35 kg were narcotized by thiopental, intubated, and placed on a volume-cycled ventilator. Anaesthesia was maintained by 1.5% sevoflurane with oxygen. Following location of the 1 st lumbar vertebra animals were fastened in an immobilization frame. The spinal cord, exposed through a laminectomy, was compressed by a 5 mm thick circular rod with a peak force of 0.8 kg at a velocity of 3 cm·s -1 . The next day the minipigs were paraplegic but improved rapidly to paraparesis. On the 12 th postoperative day they were euthanasied. Neural tissue changes were evaluated by post mortem MRI, which showed damage to the spinal cord white and/or gray matter in the epicentre of compression with longitudinal spreading over one segment cranially and caudally. Statistical analyses performed by Spearman's rho test revealed positive correlations between damaged areas and the whole area of the spinal cord white/gray matter (P = 0.047; r s = 0.742) and (P = 0.002; r s = 0.943), respectively. The study confirmed the reliability and reproducibility of the utilised model of spinal cord trauma. The structural changes in the epicentre of injury did not impede the rapid but incomplete recovery of motor functions.
Neurochemistry international, 2009
Cerebral hypoxic-ischemic injury represents a serious health problem and is the third leading cau... more Cerebral hypoxic-ischemic injury represents a serious health problem and is the third leading cause of mortality in developed countries. Early diagnosis of hypoxic-ischemic injury to the brain is inevitable for timely and efficient treatment. However, routinely applied cranial ultrasonography or computed tomography is often not sensitive enough to detect cerebral hypoxic-ischemic injury in its early stages. Therefore searching for a more effective diagnostic tool has been an intensive process in many laboratories within the last decades. Nowadays, magnetic resonance imaging (MRI) and spectroscopy (MRS) are the most promising non-invasive and non-destructive tools working in-real-time. These magnetic resonance-based techniques are progressively utilized in neurological and neonatology departments to confirm or refute cerebral hypoxic-ischemic injury in adults and neonates. The purpose of the present paper was therefore (i) to provide a brief overview on mechanisms of hypoxic-ischemic...
Agents and Actions, 1991
The potential involvement of increased mucus secretion in the antiulcer activity of a cytoprotect... more The potential involvement of increased mucus secretion in the antiulcer activity of a cytoprotective agent, pentacaine, and of the H2-antagonist ranitidine was studied in stressed rats. Cold-restraint stress decreased the gastric mucus content and induced haemorrhagic erosions in the stomach. Pretreatment with pentacaine and ranitidine dose-dependently diminished the extent of stress-induced gastric damage. Pentacaine prevented the depletion of mucus after stress, while ranitidine failed to affect it. In non-stressed rats only pentacaine was able to enhance mucus secretion. The stimulating effect of pentacaine on gastric mucus secretion may account for some of its antiulcer properties.
For a decade or two, the hypothesis of causality of various disorders by reactive oxygen species ... more For a decade or two, the hypothesis of causality of various disorders by reactive oxygen species (ROS), due to their potentially harmful effect towards cellular constituents, is one of the most frequently cited in biomedical sciences. In fact, the ROS-mediated alterations of biomacromolecules are considered to be essential events in the etiopathogenesis of those diseases where involvement of ROS has been indicated. ROS easily react in vitro with most biological molecules, causing their degradation and destruction. This may implicitly suggest that, when excessively produced in vivo, ROS are deleterious to integral components of the cell and cause their dysfunctions. Some experimental data indicate that ROS-mediated lipid peroxidation, protein oxidation and oxidative alterations to nucleic acids are crucial events of unfavorable actions of ROS. Yet the most convincing evidence, i.e. unambiguous inhibition of tissue injury by pretreatment with antioxidants, has not been provided. On the contrary, there are quite a few papers reporting failure in applying antioxidants to heal those pathologies where the causal role of ROS was supposed. Other papers reported serious complications arising from antioxidant therapy, which is quite in contradiction to its expected effect. On the other hand, an increasing number of recent findings have provided evidence of a key role of ROS in both intracellular signaling and intercellular communication, processes involved in maintaining homeostasis. Hence, some investigators consider excessive production of ROS to be rather a "smoke after the fire" than "a deleterious fire" itself, suggesting the occurrence of overproduced ROS as being the consequence of some primary damage. The present paper aims at summarizing some pros and cons of various opinions with an attempt to help better understand the involvement of ROS in tissue injury.
Carbohydrate Polymers, 2015
The ability to protect hyaluronic acid (HA) from oxidative degradation by cupric ions and ascorba... more The ability to protect hyaluronic acid (HA) from oxidative degradation by cupric ions and ascorbate (production of OH and peroxy-type radicals) during acute phase joint inflammation has been investigated using the following drugs: tiopronin, captopril, and levamisole. Radical scavenging activity, i.e. the propensity for donation of electrons was assessed for the drugs by ABTS and DPPH assays. The kinetics of HA degradation have been measured in the presence of each drug using rotational viscometry. The results of ABTS and DPPH assays show the highest radical scavenging activity for captopril, followed by tiopronin. For levamisole, no effect was observed. Captopril and tiopronin prevented HA degradation induced by OH radicals in a similar manner, while tiopronin was more effective in scavenging peroxy-type radicals. On the other hand, levamisole was shown to be a pro-oxidant. Recovered HA fragments were characterized using FT-IR analysis, the incorporation of a sulphur atom from captopril and tiopronin but not from levamisole into the HA molecule was demonstrated.
General Physiology and Biophysics
We investigated the effect of lipid peroxidation, in vitro induced by H2O2 or FeS04 and ascorbic ... more We investigated the effect of lipid peroxidation, in vitro induced by H2O2 or FeS04 and ascorbic acid, on binding properties of muscarinic receptors in rat cerebral cortex membranes. Simultaneously the concentrations of thiobarbituric acid reactive substances (TBARS) were measured to assess the extent of lipid peroxidation. In conditions of increased TBARS levels the density of ( 3 H)Nmethylscopolamine [( 3 H)NMS] binding sites in rat cerebral cortex membranes was not affected. Decreased numbers of ( 3 H)NMS binding sites observed in the presence of high concentrations of H2O2 (100 and 1000 mmol.l" 1 ) accompanied by a decrease of TBARS levels might be related to a nonspecific effect of H2O2 on cellular proteins.
Pharmacology
The present study was designed to test the hypothesis that lack of oxygen in severely hypoxic tis... more The present study was designed to test the hypothesis that lack of oxygen in severely hypoxic tissue may inhibit arachidonic acid oxygenation and thereby result in an inhibition of eicosanoid synthesis. Hypoxia was induced in the isolated rabbit ear, and arachidonate metabolism and peripheral resistance of the preparation were monitored simultaneously. Severe hypoxia completely inhibited the biosynthesis of prostaglandin I 2 induced by ionophore A23187 and converted the vasodilatory response observed under normoxia into vasoconstriction. The cyclooxygenase 1 inhibitor SC560 (1 Ìmol/l) effectively inhibited the normoxic prostaglandin I 2 biosynthesis, while the cyclooxygenase 2 inhibitor DFU (1 Ìmol/l) did not. Neither SC560 nor DFU affected normoxic vasodilatory responses, indicating no involvement of prostanoids. The nitric oxide (synthase inhibitor Nˆ-nitro-L-arginine methyl ester (100 Ìmol/l) converted the vasodilation into vasoconstriction, similar to what was observed under hypoxia, suggesting that the hypoxia-mediated conversion might occur due to the inhibition of nitric oxide.
Pharmazie
Lipid peroxidation (LPO) is one of the main events induced by oxidative stress. The aim of our st... more Lipid peroxidation (LPO) is one of the main events induced by oxidative stress. The aim of our study was to investigate the influence of 30 min cold-immobilization (model of acute stress used in this experiment) on LPO in the brain, heart, liver and stomach homogenates of the rats. LPO was determined by measuring of the contents of thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and sulfhydryl groups (SH). Experimental stress induced enhancement of TBARS formation in the liver and increased level of the CD in the heart, stomach and liver, while in the brain both parameters were found to be decreased. The levels of TBARS were not changed in the heart and in the stomach, too. The concentrations of SH-groups were decreased in the heart, brain and stomach, while in the liver the parameter was found to be not changed. The results of this study showed the increase of LPO in the heart, stomach and liver under stress conditions. It could be supposed that LPO may be i...
Central European journal of public health, 2004
The aim of the present study was to test the hypothesis that the natural antioxidant melatonin (M... more The aim of the present study was to test the hypothesis that the natural antioxidant melatonin (MEL) and the synthetic antioxidant stobadine (STO) could reduce the incidence of maternal and embryofoetal toxicity in rats due to intrauterine hypoxia. Chronic hypoxia was induced pharmacologically by the administration of the anticonvulsant phenytoin (PHT) during the entire period of pregnancy. PHT disturbed the normal course of pregnancy, affected reproductive parameters and increased the incidence of skeletal anomalies. MEL did not protect the PHT-induced development toxicity in rat. On the other hand, STO partially prevented PHT-induced reduction of foetal and placental weights. Administration of STO also decreased the frequency of pre- and post-implantation loss and resorptions in the PHT group. We concluded that pretreatment of pregnant rats with STO prevented to a certain extent reproductive and foetal development alterations caused by chronic intrauterine hypoxia.
Principles and Technological Implications, 2015
Ceskoslovenská fysiologie / Ústrední ústav biologický, 1995
The action of drugs on processes in smooth muscles, in their innervation or mucosa results in cha... more The action of drugs on processes in smooth muscles, in their innervation or mucosa results in changes in contractility of the gut, airways, vessels and urogenital system. Noteworthy insight has been gained into the basic common characteristics ot smooth muscles as well as into special properties of individual smooth muscle types whose fundamental properties have become adapted to a particular situation. This insight along with knowledge on the subcellular and cellular organization of smooth muscle cells and of their innervation, on the role of the mucosa, and introduction of sophisticated electrophysiological, biochemical, isotopic and morphological methods makes smooth muscle suitable for investigation of elemental physiological and pathophysiological processes and of targets of drug action. The complexity of the smooth muscle tissue allows to study the mechanisms of drug action on the peripheral cholinergic, adrenergic, nonadrenergic-noncholinergic nerves and their neuromediators,...
Biomedica biochimica acta, 1991
The ability of stobadine (ST) to prevent lipid peroxidation was tested in incomplete rat cerebral... more The ability of stobadine (ST) to prevent lipid peroxidation was tested in incomplete rat cerebral ischemia induced by 4 hour ligation of the common carotid arteries with a subsequent 10 min reperfusion. The extent of lipid peroxidation was determined by the measurement of the level of conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS). The levels of CD and TBARS were significantly elevated in brain cortex samples from animals subjected to ischemia followed by reoxygenation in comparison with ischemic samples without reperfusion, samples from sham operated or control animals. The concentration of CD and TBARS significantly decreased in animals treated with therapeutic doses of ST (2 mg/kg) administered i.v. immediately before reperfusion or 10 min after the onset of reperfusion. Stobadine was more effective than the known lipid antioxidant vitamin E, given in a dose of 30 mg/kg.day i.m. over 3 consecutive days prior to ischemia. The beneficial effect of ST on ...
High-molar-mass hyaluronan (HA) was used as a model biomacromolecule to study its in vitro oxidat... more High-molar-mass hyaluronan (HA) was used as a model biomacromolecule to study its in vitro oxidative damage. The main aim of the present study was to test Aloe Vera Freedom drinking gel and one of its components, methylsulfonylmethane, for their ability to protect HA from oxidative degradation. The secondary objective was to monitor the blood glucose levels in a patient suffering from osteoarthritis and type II diabetes mellitus and taking Aloe Vera Freedom drinking gel. The oxidative degradation of high-molar-mass HA in vitro was initiated by the Weissberger system, comprising ascorbate and cupric ions, and monitored by rotational viscometry. The pro- and antioxidative activity of methylsulfonylmethane was determined by ABTS and DPPH decolorization assays. The patient's glycemia was monitored using a conventional glucometer for 41 days. Dose-dependent protection of high-molar-mass HA from its oxidative degradation by Aloe Vera Freedom drinking gel was found. Methylsulfonylmetha...
Five hexahydropyridoindoles, namely stobadine, SM1dM9dM10, SME1i-ProC2, SM1M3EC2, and SMe1EC2, in... more Five hexahydropyridoindoles, namely stobadine, SM1dM9dM10, SME1i-ProC2, SM1M3EC2, and SMe1EC2, in the form of mono- or dihydrochloride salts, were tested to act as an H atom donor as well as an electron donor. The H atom donating properties of the substances were examined by rotational viscometry - an assay based on hyaluronan free-radical degradation induced by ascorbate plus Cu(II) under aerobic conditions. For evaluating the electron donor properties of the substances, the standard ABTS and DPPH decolorization assays were applied. Results of rotational viscometry showed that in time 1 h and 5 h the most effective preventive antioxidants were stobadine and SME1i-ProC2, respectively. The most effective chain-breaking antioxidant was recorded to be stobadine. The efficacy of the substances analyzed by the ABTS assay increased in the order: SM1M3EC2 > stobadine > SMe1EC2 > SME1i-ProC2 > SM1dM9dM10. Yet, the latter substance demonstrated a prooxidative effect on assaying i...
Chemical Papers, 2014
ABSTRACT Oxidative stress and the resulting damage to cellular and extracellular components has b... more ABSTRACT Oxidative stress and the resulting damage to cellular and extracellular components has been observed in a variety of degenerative processes, including degenerative joint disorders, where high-molar-mass hyaluronan (HA) is often found to be massively degraded. The present study sought to test the hypothesis that dithiols are more effective in protecting biomacromolecules from free-radicalmediated damage than monothiols. The materials/thiols tested included bucillamine (BUC), dithioerythritol (DTE), dithiothreitol (DTT) and glutathione (GSH), as a reference, for their effectiveness in protecting HA from oxidative degradation induced in vitro. Since HA degradation results in a decrease in its dynamic viscosity, rotational viscometry was applied to follow HA oxidative degradation. The free-radical-scavenging activities of the thiols tested were determined by 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) and di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH) assays. It was found that all the dithiols in the concentration range tested protected HA from the oxidative degradation. On the other hand, monothiol GSH exerted protection only at high concentrations (10 μmol L−1 and 100 μmol L−1) and 1 μmol L−1 of GSH even exhibited a prodegradative effect. The ABTS assay revealed free-radical scavenging activities in the following order: BUC, DTT, DTE, GSH, and that of the DPPH assay: BUC, DTE, DTT, GSH. In conclusion, it was demonstrated that dithiols may be more effective than monothiols in affording biomacromolecule protection from oxidative degradation.
General physiology and biophysics, 2005
For a decade or two, the hypothesis of causality of various disorders by reactive oxygen species ... more For a decade or two, the hypothesis of causality of various disorders by reactive oxygen species (ROS), due to their potentially harmful effect towards cellular constituents, is one of the most frequently cited in biomedical sciences. In fact, the ROS-mediated alterations of biomacromolecules are considered to be essential events in the etiopathogenesis of those diseases where involvement of ROS has been indicated. ROS easily react in vitro with most biological molecules, causing their degradation and destruction. This may implicitly suggest that, when excessively produced in vivo, ROS are deleterious to integral components of the cell and cause their dysfunctions. Some experimental data indicate that ROS-mediated lipid peroxidation, protein oxidation and oxidative alterations to nucleic acids are crucial events of unfavorable actions of ROS. Yet the most convincing evidence, i.e. unambiguous inhibition of tissue injury by pretreatment with antioxidants, has not been provided. On th...
Central European journal of public health, 2004
The present study was designed to investigate mechanisms of adenosine (ADO)-mediated prolongation... more The present study was designed to investigate mechanisms of adenosine (ADO)-mediated prolongation of conductivity through the atrioventricular (AV) node during myocardial ischemia. Using the Langendorff preparation of the guinea pig heart, we tested the hypothesis that extracellular potassium concentration elevated due to ischemia could augment ADO effect. Exposure of the heart preparation to either stop-flow or hypoxic Krebs-Henseleit solution (KH) inhibited AV node conductivity observed as an increase in SH interval, and finally resulted in AV block. Superficial potassium concentration ([K+]s), recorded simultaneously increased in response to each stop-flow or hypoxia. Application of 0.1 mM BaCl2 markedly increased the SH interval, yet it did neither protect the heart from hypoxia-evoked AV block nor did it prevent hypoxia-induced [K+]s elevation. Neither did perfusion of the myocardium with modified KH containing 8 mM K+ affect the hypoxic AV block and [K+]s increase. The hypoxic...
Die Pharmazie, 1995
The effect of selected carbanilates on the rat gastric mucus was tested after oral administration... more The effect of selected carbanilates on the rat gastric mucus was tested after oral administration. The compounds K 1905 and K 2002 were found to increase gastric mucus content in nonstressed rats while compound P 2 was ineffective. The activity of K 1905 was comparable with that of the parent drug trapencaine. Cold-restraint stress decreased the gastric mucus content and induced haemorrhagic erosions in the glandular stomach. With the exception of compound P 2 pretreatment with carbanilates dose-dependently diminished the extent of stress-induced gastric damage and prevented the depletion of mucus after stress. The results indicate that pentyloxy-substitution in the meta and in the para position on the benzene ring of the parent structure (K 1905 and K 2002, respectively) seems to be more suitable for mucus enhancing activity than alkyloxy-substitution on the para position (P 2). The observed increased mucus secretion might be partly responsible for the gastroprotective action of th...
Acta Veterinaria Brno, 2014
The study concentrated on behavioral and magnetic resonance imaging (MRI) characteristics in a po... more The study concentrated on behavioral and magnetic resonance imaging (MRI) characteristics in a porcine spinal cord injury model. Six adult minipigs weighing 32-35 kg were narcotized by thiopental, intubated, and placed on a volume-cycled ventilator. Anaesthesia was maintained by 1.5% sevoflurane with oxygen. Following location of the 1 st lumbar vertebra animals were fastened in an immobilization frame. The spinal cord, exposed through a laminectomy, was compressed by a 5 mm thick circular rod with a peak force of 0.8 kg at a velocity of 3 cm·s -1 . The next day the minipigs were paraplegic but improved rapidly to paraparesis. On the 12 th postoperative day they were euthanasied. Neural tissue changes were evaluated by post mortem MRI, which showed damage to the spinal cord white and/or gray matter in the epicentre of compression with longitudinal spreading over one segment cranially and caudally. Statistical analyses performed by Spearman's rho test revealed positive correlations between damaged areas and the whole area of the spinal cord white/gray matter (P = 0.047; r s = 0.742) and (P = 0.002; r s = 0.943), respectively. The study confirmed the reliability and reproducibility of the utilised model of spinal cord trauma. The structural changes in the epicentre of injury did not impede the rapid but incomplete recovery of motor functions.
Neurochemistry international, 2009
Cerebral hypoxic-ischemic injury represents a serious health problem and is the third leading cau... more Cerebral hypoxic-ischemic injury represents a serious health problem and is the third leading cause of mortality in developed countries. Early diagnosis of hypoxic-ischemic injury to the brain is inevitable for timely and efficient treatment. However, routinely applied cranial ultrasonography or computed tomography is often not sensitive enough to detect cerebral hypoxic-ischemic injury in its early stages. Therefore searching for a more effective diagnostic tool has been an intensive process in many laboratories within the last decades. Nowadays, magnetic resonance imaging (MRI) and spectroscopy (MRS) are the most promising non-invasive and non-destructive tools working in-real-time. These magnetic resonance-based techniques are progressively utilized in neurological and neonatology departments to confirm or refute cerebral hypoxic-ischemic injury in adults and neonates. The purpose of the present paper was therefore (i) to provide a brief overview on mechanisms of hypoxic-ischemic...
Agents and Actions, 1991
The potential involvement of increased mucus secretion in the antiulcer activity of a cytoprotect... more The potential involvement of increased mucus secretion in the antiulcer activity of a cytoprotective agent, pentacaine, and of the H2-antagonist ranitidine was studied in stressed rats. Cold-restraint stress decreased the gastric mucus content and induced haemorrhagic erosions in the stomach. Pretreatment with pentacaine and ranitidine dose-dependently diminished the extent of stress-induced gastric damage. Pentacaine prevented the depletion of mucus after stress, while ranitidine failed to affect it. In non-stressed rats only pentacaine was able to enhance mucus secretion. The stimulating effect of pentacaine on gastric mucus secretion may account for some of its antiulcer properties.
For a decade or two, the hypothesis of causality of various disorders by reactive oxygen species ... more For a decade or two, the hypothesis of causality of various disorders by reactive oxygen species (ROS), due to their potentially harmful effect towards cellular constituents, is one of the most frequently cited in biomedical sciences. In fact, the ROS-mediated alterations of biomacromolecules are considered to be essential events in the etiopathogenesis of those diseases where involvement of ROS has been indicated. ROS easily react in vitro with most biological molecules, causing their degradation and destruction. This may implicitly suggest that, when excessively produced in vivo, ROS are deleterious to integral components of the cell and cause their dysfunctions. Some experimental data indicate that ROS-mediated lipid peroxidation, protein oxidation and oxidative alterations to nucleic acids are crucial events of unfavorable actions of ROS. Yet the most convincing evidence, i.e. unambiguous inhibition of tissue injury by pretreatment with antioxidants, has not been provided. On the contrary, there are quite a few papers reporting failure in applying antioxidants to heal those pathologies where the causal role of ROS was supposed. Other papers reported serious complications arising from antioxidant therapy, which is quite in contradiction to its expected effect. On the other hand, an increasing number of recent findings have provided evidence of a key role of ROS in both intracellular signaling and intercellular communication, processes involved in maintaining homeostasis. Hence, some investigators consider excessive production of ROS to be rather a "smoke after the fire" than "a deleterious fire" itself, suggesting the occurrence of overproduced ROS as being the consequence of some primary damage. The present paper aims at summarizing some pros and cons of various opinions with an attempt to help better understand the involvement of ROS in tissue injury.
Carbohydrate Polymers, 2015
The ability to protect hyaluronic acid (HA) from oxidative degradation by cupric ions and ascorba... more The ability to protect hyaluronic acid (HA) from oxidative degradation by cupric ions and ascorbate (production of OH and peroxy-type radicals) during acute phase joint inflammation has been investigated using the following drugs: tiopronin, captopril, and levamisole. Radical scavenging activity, i.e. the propensity for donation of electrons was assessed for the drugs by ABTS and DPPH assays. The kinetics of HA degradation have been measured in the presence of each drug using rotational viscometry. The results of ABTS and DPPH assays show the highest radical scavenging activity for captopril, followed by tiopronin. For levamisole, no effect was observed. Captopril and tiopronin prevented HA degradation induced by OH radicals in a similar manner, while tiopronin was more effective in scavenging peroxy-type radicals. On the other hand, levamisole was shown to be a pro-oxidant. Recovered HA fragments were characterized using FT-IR analysis, the incorporation of a sulphur atom from captopril and tiopronin but not from levamisole into the HA molecule was demonstrated.
General Physiology and Biophysics
We investigated the effect of lipid peroxidation, in vitro induced by H2O2 or FeS04 and ascorbic ... more We investigated the effect of lipid peroxidation, in vitro induced by H2O2 or FeS04 and ascorbic acid, on binding properties of muscarinic receptors in rat cerebral cortex membranes. Simultaneously the concentrations of thiobarbituric acid reactive substances (TBARS) were measured to assess the extent of lipid peroxidation. In conditions of increased TBARS levels the density of ( 3 H)Nmethylscopolamine [( 3 H)NMS] binding sites in rat cerebral cortex membranes was not affected. Decreased numbers of ( 3 H)NMS binding sites observed in the presence of high concentrations of H2O2 (100 and 1000 mmol.l" 1 ) accompanied by a decrease of TBARS levels might be related to a nonspecific effect of H2O2 on cellular proteins.
Pharmacology
The present study was designed to test the hypothesis that lack of oxygen in severely hypoxic tis... more The present study was designed to test the hypothesis that lack of oxygen in severely hypoxic tissue may inhibit arachidonic acid oxygenation and thereby result in an inhibition of eicosanoid synthesis. Hypoxia was induced in the isolated rabbit ear, and arachidonate metabolism and peripheral resistance of the preparation were monitored simultaneously. Severe hypoxia completely inhibited the biosynthesis of prostaglandin I 2 induced by ionophore A23187 and converted the vasodilatory response observed under normoxia into vasoconstriction. The cyclooxygenase 1 inhibitor SC560 (1 Ìmol/l) effectively inhibited the normoxic prostaglandin I 2 biosynthesis, while the cyclooxygenase 2 inhibitor DFU (1 Ìmol/l) did not. Neither SC560 nor DFU affected normoxic vasodilatory responses, indicating no involvement of prostanoids. The nitric oxide (synthase inhibitor Nˆ-nitro-L-arginine methyl ester (100 Ìmol/l) converted the vasodilation into vasoconstriction, similar to what was observed under hypoxia, suggesting that the hypoxia-mediated conversion might occur due to the inhibition of nitric oxide.
Pharmazie
Lipid peroxidation (LPO) is one of the main events induced by oxidative stress. The aim of our st... more Lipid peroxidation (LPO) is one of the main events induced by oxidative stress. The aim of our study was to investigate the influence of 30 min cold-immobilization (model of acute stress used in this experiment) on LPO in the brain, heart, liver and stomach homogenates of the rats. LPO was determined by measuring of the contents of thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and sulfhydryl groups (SH). Experimental stress induced enhancement of TBARS formation in the liver and increased level of the CD in the heart, stomach and liver, while in the brain both parameters were found to be decreased. The levels of TBARS were not changed in the heart and in the stomach, too. The concentrations of SH-groups were decreased in the heart, brain and stomach, while in the liver the parameter was found to be not changed. The results of this study showed the increase of LPO in the heart, stomach and liver under stress conditions. It could be supposed that LPO may be i...
Central European journal of public health, 2004
The aim of the present study was to test the hypothesis that the natural antioxidant melatonin (M... more The aim of the present study was to test the hypothesis that the natural antioxidant melatonin (MEL) and the synthetic antioxidant stobadine (STO) could reduce the incidence of maternal and embryofoetal toxicity in rats due to intrauterine hypoxia. Chronic hypoxia was induced pharmacologically by the administration of the anticonvulsant phenytoin (PHT) during the entire period of pregnancy. PHT disturbed the normal course of pregnancy, affected reproductive parameters and increased the incidence of skeletal anomalies. MEL did not protect the PHT-induced development toxicity in rat. On the other hand, STO partially prevented PHT-induced reduction of foetal and placental weights. Administration of STO also decreased the frequency of pre- and post-implantation loss and resorptions in the PHT group. We concluded that pretreatment of pregnant rats with STO prevented to a certain extent reproductive and foetal development alterations caused by chronic intrauterine hypoxia.
Principles and Technological Implications, 2015
Ceskoslovenská fysiologie / Ústrední ústav biologický, 1995
The action of drugs on processes in smooth muscles, in their innervation or mucosa results in cha... more The action of drugs on processes in smooth muscles, in their innervation or mucosa results in changes in contractility of the gut, airways, vessels and urogenital system. Noteworthy insight has been gained into the basic common characteristics ot smooth muscles as well as into special properties of individual smooth muscle types whose fundamental properties have become adapted to a particular situation. This insight along with knowledge on the subcellular and cellular organization of smooth muscle cells and of their innervation, on the role of the mucosa, and introduction of sophisticated electrophysiological, biochemical, isotopic and morphological methods makes smooth muscle suitable for investigation of elemental physiological and pathophysiological processes and of targets of drug action. The complexity of the smooth muscle tissue allows to study the mechanisms of drug action on the peripheral cholinergic, adrenergic, nonadrenergic-noncholinergic nerves and their neuromediators,...
Biomedica biochimica acta, 1991
The ability of stobadine (ST) to prevent lipid peroxidation was tested in incomplete rat cerebral... more The ability of stobadine (ST) to prevent lipid peroxidation was tested in incomplete rat cerebral ischemia induced by 4 hour ligation of the common carotid arteries with a subsequent 10 min reperfusion. The extent of lipid peroxidation was determined by the measurement of the level of conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS). The levels of CD and TBARS were significantly elevated in brain cortex samples from animals subjected to ischemia followed by reoxygenation in comparison with ischemic samples without reperfusion, samples from sham operated or control animals. The concentration of CD and TBARS significantly decreased in animals treated with therapeutic doses of ST (2 mg/kg) administered i.v. immediately before reperfusion or 10 min after the onset of reperfusion. Stobadine was more effective than the known lipid antioxidant vitamin E, given in a dose of 30 mg/kg.day i.m. over 3 consecutive days prior to ischemia. The beneficial effect of ST on ...
High-molar-mass hyaluronan (HA) was used as a model biomacromolecule to study its in vitro oxidat... more High-molar-mass hyaluronan (HA) was used as a model biomacromolecule to study its in vitro oxidative damage. The main aim of the present study was to test Aloe Vera Freedom drinking gel and one of its components, methylsulfonylmethane, for their ability to protect HA from oxidative degradation. The secondary objective was to monitor the blood glucose levels in a patient suffering from osteoarthritis and type II diabetes mellitus and taking Aloe Vera Freedom drinking gel. The oxidative degradation of high-molar-mass HA in vitro was initiated by the Weissberger system, comprising ascorbate and cupric ions, and monitored by rotational viscometry. The pro- and antioxidative activity of methylsulfonylmethane was determined by ABTS and DPPH decolorization assays. The patient's glycemia was monitored using a conventional glucometer for 41 days. Dose-dependent protection of high-molar-mass HA from its oxidative degradation by Aloe Vera Freedom drinking gel was found. Methylsulfonylmetha...
Five hexahydropyridoindoles, namely stobadine, SM1dM9dM10, SME1i-ProC2, SM1M3EC2, and SMe1EC2, in... more Five hexahydropyridoindoles, namely stobadine, SM1dM9dM10, SME1i-ProC2, SM1M3EC2, and SMe1EC2, in the form of mono- or dihydrochloride salts, were tested to act as an H atom donor as well as an electron donor. The H atom donating properties of the substances were examined by rotational viscometry - an assay based on hyaluronan free-radical degradation induced by ascorbate plus Cu(II) under aerobic conditions. For evaluating the electron donor properties of the substances, the standard ABTS and DPPH decolorization assays were applied. Results of rotational viscometry showed that in time 1 h and 5 h the most effective preventive antioxidants were stobadine and SME1i-ProC2, respectively. The most effective chain-breaking antioxidant was recorded to be stobadine. The efficacy of the substances analyzed by the ABTS assay increased in the order: SM1M3EC2 > stobadine > SMe1EC2 > SME1i-ProC2 > SM1dM9dM10. Yet, the latter substance demonstrated a prooxidative effect on assaying i...
Chemical Papers, 2014
ABSTRACT Oxidative stress and the resulting damage to cellular and extracellular components has b... more ABSTRACT Oxidative stress and the resulting damage to cellular and extracellular components has been observed in a variety of degenerative processes, including degenerative joint disorders, where high-molar-mass hyaluronan (HA) is often found to be massively degraded. The present study sought to test the hypothesis that dithiols are more effective in protecting biomacromolecules from free-radicalmediated damage than monothiols. The materials/thiols tested included bucillamine (BUC), dithioerythritol (DTE), dithiothreitol (DTT) and glutathione (GSH), as a reference, for their effectiveness in protecting HA from oxidative degradation induced in vitro. Since HA degradation results in a decrease in its dynamic viscosity, rotational viscometry was applied to follow HA oxidative degradation. The free-radical-scavenging activities of the thiols tested were determined by 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) and di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH) assays. It was found that all the dithiols in the concentration range tested protected HA from the oxidative degradation. On the other hand, monothiol GSH exerted protection only at high concentrations (10 μmol L−1 and 100 μmol L−1) and 1 μmol L−1 of GSH even exhibited a prodegradative effect. The ABTS assay revealed free-radical scavenging activities in the following order: BUC, DTT, DTE, GSH, and that of the DPPH assay: BUC, DTE, DTT, GSH. In conclusion, it was demonstrated that dithiols may be more effective than monothiols in affording biomacromolecule protection from oxidative degradation.