jan slezak - Academia.edu (original) (raw)
Papers by jan slezak
International Journal of Molecular Sciences, 2019
Heart function and its susceptibility to arrhythmias are modulated by thyroid hormones (THs) but ... more Heart function and its susceptibility to arrhythmias are modulated by thyroid hormones (THs) but the responsiveness of hypertensive individuals to thyroid dysfunction is elusive. We aimed to explore the effect of altered thyroid status on crucial factors affecting synchronized heart function, i.e., connexin-43 (Cx43) and extracellular matrix proteins (ECM), in spontaneously hypertensive rats (SHRs) compared to normotensive Wistar Kyoto rats (WKRs). Basal levels of circulating THs were similar in both strains. Hyperthyroid state (HT) was induced by injection of T3 (0.15 mg/kg b.w. for eight weeks) and hypothyroid state (HY) by the administration of methimazol (0.05% for eight weeks). The possible benefit of omega-3 polyunsaturated fatty acids (Omacor, 200 mg/kg for eight weeks) intake was examined as well. Reduced levels of Cx43 in SHRs were unaffected by alterations in THs, unlike WKRs, in which levels of Cx43 and its phosphorylated form at serine368 were decreased in the HT state a...
Antioxidants
Non-alcoholic fatty liver disease (NAFLD) is a liver pathology affecting around 25% of the popula... more Non-alcoholic fatty liver disease (NAFLD) is a liver pathology affecting around 25% of the population worldwide. Excess oxidative stress, inflammation and aberrant cellular signaling can lead to this hepatic dysfunction and eventual carcinoma. Molecular hydrogen has been recognized for its selective antioxidant properties and ability to attenuate inflammation and regulate cellular function. We administered hydrogen-rich water (HRW) to 30 subjects with NAFLD in a randomized, double-blinded, placebo-controlled manner for eight weeks. Phenotypically, we observed beneficial trends (p > 0.05) in decreased weight (≈1 kg) and body mass index in the HRW group. HRW was well-tolerated, with no significant changes in liver enzymes and a trend of improved lipid profile and reduced lactate dehydrogenase levels. HRW tended to non-significantly decrease levels of nuclear factor kappa B, heat shock protein 70 and matrix metalloproteinase-9. Interestingly, there was a mild, albeit non-significant...
Cardiovascular Research, 2018
differentiated in cardiogenic, adipogenic and osteogenic directions by addition of specific induc... more differentiated in cardiogenic, adipogenic and osteogenic directions by addition of specific inducers to the cell culture medium. Differentiation efficiency was estimated by qPCR for specific markers of differentiation. Differentiated cells were stained for the specific markers by immunocytochemistry. Results: Peri-infarct cells possessed a higher proliferative potential than the cells from healthy area of the myocardium. They also had a greater propensity to migrate to the area of a "scratch". According to a PCR experiment, the level of activation of specific differentiation markers (TNNT2, BMP2, Runx2 and Fabp4) was higher in peri-infarct cells. Conclusion: Ischemic damage of the myocardium leads to activation of the internal regenerative potential of cardiac stem cells in vivo, which is most pronounced in the peri-infarction zone. P259 Up-regulation of myocardial connexin-43 is involved in compensatory response of the heart to acute injury
Current Pharmaceutical Design, 2021
There are many situations of excessive production of reactive oxygen species (ROS) such as radiat... more There are many situations of excessive production of reactive oxygen species (ROS) such as radiation, ischemia/reperfusion (I/R), and inflammation. ROS contribute to and arises from numerous cellular pathologies, diseases, and aging. ROS can cause direct deleterious effects by damaging proteins, lipids, and nucleic acids as well as exert detrimental effects on several cell signaling pathways. However, ROS are important in many cellular functions. The injurious effect of excessive ROS can hypothetically be mitigated by exogenous antioxidants, but clinically this intervention is often not favorable. In contrast, molecular hydrogen provides a variety of advantages for mitigating oxidative stress due to its unique physical and chemical properties. H2 may be superior to conventional antioxidants, since it can selectively reduce ●OH radicals while preserving important ROS that are otherwise used for normal cellular signaling. Additionally, H2 exerts many biological effects, including anti...
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 2020
Purpose: Metabolic syndrome is associated with several medical risk factors including dyslipidemi... more Purpose: Metabolic syndrome is associated with several medical risk factors including dyslipidemia, hyperglycemia, and obesity, which has become a worldwide pandemic. The sequelae of this condition increase the risk of cardiovascular and neurological disease and increased mortality. Its pathophysiology is associated with redox dysregulation, excessive inflammation, and perturbation of cellular homeostasis. Molecular hydrogen (H 2) may attenuate oxidative stress, improve cellular function, and reduce chronic inflammation. Preclinical and clinical studies have shown promising effects of H 2-rich water (HRW) on specific features of metabolic syndrome, yet the effects of long-term, high-concentration HRW in this prevalent condition remain poorly addressed. Methods: We conducted a randomized, double-blinded, placebo-controlled trial in 60 subjects (30 men and 30 women) with metabolic syndrome. An initial observation period of one week was used to acquire baseline clinical data followed by randomization to either placebo or high-concentration HRW (> 5.5 millimoles of H 2 per day) for 24 weeks. Results: Supplementation with high-concentration HRW significantly reduced blood cholesterol and glucose levels, attenuated serum hemoglobin A1c, and improved biomarkers of inflammation and redox homeostasis as compared to placebo (P < 0.05). Furthermore, H 2 tended to promote a mild reduction in body mass index and waist-to-hip ratio. Conclusion: Our results give further credence that high-concentration HRW might have promising effects as a therapeutic modality for attenuating risk factors of metabolic syndrome.
Physiological Research, 2016
Remote ischemic preconditioning (RIPC) is a novel strategy of protection against ischemia-reperfu... more Remote ischemic preconditioning (RIPC) is a novel strategy of protection against ischemia-reperfusion (IR) injury in the heart (and/or other organs) by brief episodes of non-lethal IR in a distant organ/tissue. Importantly, RIPC can be induced noninvasively by limitation of blood flow in the extremity implying the applicability of this method in clinical situations. RIPC (and its delayed phase) is a form of relatively short-term adaptation to ischemia, similar to ischemic PC, and likely they both share triggering mechanisms, whereas mediators and end-effectors may differ. It is hypothesized that communication between the signals triggered in the remote organs and protection in the target organ may be mediated through substances released from the preconditioned organ and transported via the circulation (humoral pathways), by neural pathways and/or via systemic anti-inflammatory and antiapoptotic response to short ischemic bouts. Identification of molecules involved in RIPC cascades m...
Journal of Hypertension, 2019
After measuring the body mass index, waist circumference and heart rate, the two therapy groups w... more After measuring the body mass index, waist circumference and heart rate, the two therapy groups were confronted, both genders, had not found the statistically signifi cant difference. The results of CHPs (Central Aortic Pressure, End-Systolic Pressure, Mean Arterial Pressure, Pulse Pressure, Augmentation Pressure), Diff-AIx, systolic and diastolic blood pressure during association of ARBs+MRAs therapy compared to ARBs+CCBs, both genders, showed the lowest values with a highly statistically signifi cant difference. Conclusions: These fi ndings provide evidence that ARBs+MRAs treatment reaches best haemodynamic conditions because improve the arterial stiffness (Diff-AIx) and levels of pressures (CHPs) with the intention of giving to arterialventricular coupling an adequate reducing the stress.
Nutrients, 2017
Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaeno... more Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are permanent subjects of interest in relation to the protection of cardiovascular health and the prevention of the incidence of both ventricular and atrial arrhythmias. The purpose of this updated review is to focus on the novel cellular and molecular effects of omega-3 PUFAs, in the context of the mechanisms and factors involved in the development of cardiac arrhythmias; to provide results of the most recent studies on the omega-3 PUFA anti-arrhythmic efficacy and to discuss the lack of the benefit in relation to omega-3 PUFA status. The evidence is in the favor of omega-3 PUFA acute and long-term treatment, perhaps with mitochondria-targeted antioxidants. However, for a more objective evaluation of the anti-arrhythmic potential of omega-3 PUFAs in clinical trials, it is necessary to monitor the basal pre-interventional omega-3 status of individuals, i.e., red blood cell content, omega-3 index and free plasma levels. In the view of evidence-based medicine, it seems to be crucial to aim to establish new approaches in the prevention of cardiac arrhythmias and associated morbidity and mortality that comes with these conditions.
Bratislavské lekárske listy, 1974
European Heart Journal, 2013
Treatment of hypertension 269 agement studies of its kind resulted in significantly enhanced leve... more Treatment of hypertension 269 agement studies of its kind resulted in significantly enhanced levels of BP control. Applying refined strategies to optimise the potential of this type of intervention (including overcoming prescription resistance) are of clinical importance to optimise BP control.
Canadian Journal of Physiology and Pharmacology, 2018
Uncontrolled production of oxygen and nitrogen radicals results in oxidative and nitrosative stre... more Uncontrolled production of oxygen and nitrogen radicals results in oxidative and nitrosative stresses that impair cellular functions and have been regarded as causative common denominators of many pathological processes. In this review, we report on the beneficial effects of molecular hydrogen in scavenging radicals in an artificial system of•OH formation. As a proof of principle, we also demonstrate that in rat hearts in vivo, administration of molecular hydrogen led to a significant increase in superoxide dismutase as well as pAKT, a cell survival signaling molecule. Irradiation of the rats caused a significant increase in lipid peroxidation, which was mitigated by pre-treatment of the animals with molecular hydrogen. The nuclear factor erythroid 2-related factor 2 is regarded as an important regulator of oxyradical homeostasis, as well as it supports the functional integrity of cells, particularly under conditions of oxidative stress. We suggest that the beneficial effects of mol...
Histochemistry, 1985
Cerium was applied for the ultrastructural, cytochemical localization of adenylate cyclase (EC 4.... more Cerium was applied for the ultrastructural, cytochemical localization of adenylate cyclase (EC 4.6.1.1.). The enzyme activity was stimulated with norepinephrine, prenalterol and cholera toxin in the brown fat cells of newborn rats. The final reaction product was observed in the plasmalemmas of the stimulated adipocytes. The precipitate was finely crystalline, easily visible in the electron microscope and in the X-ray microprobe analysis it yielded cerium and phosphate peaks, respectively. The use of cerium offers a new tool valid for the cytochemical localization of adenylate cyclase enzyme related to the membrane receptors.
Colitis is an inflammatory condition of the bowels associated with abdominal pain, diarrhea, fati... more Colitis is an inflammatory condition of the bowels associated with abdominal pain, diarrhea, fatigue, and fever. Its etiology is multifactorial but related to the overproduction of inflammatory and oxidative mediators. There is currently no cure for this disease, and drugs used to manage it often have deleterious side effects. H2 is recognized as having anti-inflammatory and antioxidant effects, which may qualify it as a novel therapeutic for colitis. We induced an acute model of colitis in mice by administering dextran sulfate sodium (DSS) in drinking water for seven days. Mice were divided into five groups (n=6); normal, colitis, H2-treated colitis, sulfasalazine-treated colitis, and H2 plus sulfasalazine-treated colitis. From days three to ten, mice were given H2, sulfasalazine, or both. H2 was administered via dissolving a hydrogen-generating tablet in water to make hydrogen-rich water (HRW), which was ingested ad libitum and via oral gavage (200 μL). The Disease Activity Index ...
Physiological Research, Sep 15, 2016
Excessive production of oxygen free radicals has been regarded as a causative common denominator ... more Excessive production of oxygen free radicals has been regarded as a causative common denominator of many pathological processes in the animal kingdom. Hydroxyl and nitrosyl radicals represent the major cause of the destruction of biomolecules either by a direct reaction or by triggering a chain reaction of free radicals. Scavenging of free radicals may act preventively or therapeutically. A number of substances that preferentially react with free radicals can serve as scavengers, thus increasing the internal capacity/activity of endogenous antioxidants and protecting cells and tissues against oxidative damage. Molecular hydrogen (H2) reacts with strong oxidants, such as hydroxyl and nitrosyl radicals, in the cells, that enables utilization of its potential for preventive and therapeutic applications. H2 rapidly diffuses into tissues and cells without affecting metabolic redox reactions and signaling reactive species. H2 reduces oxidative stress also by regulating gene expression, and functions as an anti-inflammatory and anti-apoptotic agent. There is a growing body of evidence based on the results of animal experiments and clinical observations that H2 may represent an effective antioxidant for the prevention of oxidative stress-related diseases. Application of molecular hydrogen in situations with excessive production of free radicals, in particular, hydroxyl and nitrosyl radicals is relatively simple and effective, therefore, it deserves special attention.
Journal of Molecular and Cellular Cardiology, 1991
Antioxidants
Cardiac β-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, ... more Cardiac β-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, and fibrosis rendering the heart vulnerable to malignant arrhythmias. We aimed to explore the anti-arrhythmic efficacy of the anti-oxidative and anti-inflammatory compounds, melatonin, and omega-3, and their mechanisms of actions in normotensive and hypertensive rats exposed to isoproterenol (ISO) induced β-adrenergic overdrive. Eight-month-old, male SHR, and Wistar rats were injected during 7 days with ISO (cumulative dose, 118 mg/kg). ISO rats were either untreated or concomitantly treated with melatonin (10 mg/kg/day) or omega-3 (Omacor, 1.68 g/kg/day) until 60 days of ISO withdrawal and compared to non-ISO controls. Findings showed that both melatonin and omega-3 increased threshold current to induce ventricular fibrillation (VF) in ISO rats regardless of the strain. Prolonged treatment with these compounds resulted in significant suppression of ISO-induced extracellular matrix alter...
Antioxidants
The increased production of reactive oxygen species and oxidative stress are important factors co... more The increased production of reactive oxygen species and oxidative stress are important factors contributing to the development of diseases of the cardiovascular and central nervous systems. Molecular hydrogen is recognized as an emerging therapeutic, and its positive effects in the treatment of pathologies have been documented in both experimental and clinical studies. The therapeutic potential of hydrogen is attributed to several major molecular mechanisms. This review focuses on the effects of hydrogen on the cardiovascular and central nervous systems, and summarizes current knowledge about its actions, including the regulation of redox and intracellular signaling, alterations in gene expressions, and modulation of cellular responses (e.g., autophagy, apoptosis, and tissue remodeling). We summarize the functions of hydrogen as a regulator of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated redox signaling and the association of hydrogen with mitochondria as an important...
Biomolecules
MicroRNAs (miRNAs/miRs) such as miR-1, miR-133a, miR-133b, miR-135a, and miR-29b play a key role ... more MicroRNAs (miRNAs/miRs) such as miR-1, miR-133a, miR-133b, miR-135a, and miR-29b play a key role in many cardiac pathological remodeling processes, including apoptosis, fibrosis, and arrhythmias, after a myocardial infarction (MI). Dietary flaxseed has demonstrated a protective effect against an MI. The present study was carried out to test the hypothesis that dietary flaxseed supplementation before and after an MI regulates the expression of above-mentioned miRNAs to produce its cardioprotective effect. Animals were randomized after inducing MI by coronary artery ligation into: (a) sham MI with normal chow, (b) MI with normal chow, and (c–e) MI supplemented with either 10% milled flaxseed, or 4.4% flax oil enriched in alpha-linolenic acid (ALA), or 0.44% flax lignan secoisolariciresinol diglucoside. The feeding protocol consisted of 2 weeks before and 8 weeks after the surgery. Dietary flax oil supplementation selectively upregulated the cardiac expression of miR-133a, miR-135a, an...
International Journal of Molecular Sciences
Reactive oxygen species (ROS) are important molecules in the living organisms as a part of many s... more Reactive oxygen species (ROS) are important molecules in the living organisms as a part of many signaling pathways. However, if overproduced, they also play a significant role in the development of cardiovascular diseases, such as arrhythmia, cardiomyopathy, ischemia/reperfusion injury (e.g., myocardial infarction and heart transplantation), and heart failure. As a result of oxidative stress action, apoptosis, hypertrophy, and fibrosis may occur. MicroRNAs (miRNAs) represent important endogenous nucleotides that regulate many biological processes, including those involved in heart damage caused by oxidative stress. Oxidative stress can alter the expression level of many miRNAs. These changes in miRNA expression occur mainly via modulation of nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuins, calcineurin/nuclear factor of activated T cell (NFAT), or nuclear factor kappa B (NF-κB) pathways. Up until now, several circulating miRNAs have been reported to be potential biomarke...
International Journal of Molecular Sciences, 2019
Heart function and its susceptibility to arrhythmias are modulated by thyroid hormones (THs) but ... more Heart function and its susceptibility to arrhythmias are modulated by thyroid hormones (THs) but the responsiveness of hypertensive individuals to thyroid dysfunction is elusive. We aimed to explore the effect of altered thyroid status on crucial factors affecting synchronized heart function, i.e., connexin-43 (Cx43) and extracellular matrix proteins (ECM), in spontaneously hypertensive rats (SHRs) compared to normotensive Wistar Kyoto rats (WKRs). Basal levels of circulating THs were similar in both strains. Hyperthyroid state (HT) was induced by injection of T3 (0.15 mg/kg b.w. for eight weeks) and hypothyroid state (HY) by the administration of methimazol (0.05% for eight weeks). The possible benefit of omega-3 polyunsaturated fatty acids (Omacor, 200 mg/kg for eight weeks) intake was examined as well. Reduced levels of Cx43 in SHRs were unaffected by alterations in THs, unlike WKRs, in which levels of Cx43 and its phosphorylated form at serine368 were decreased in the HT state a...
Antioxidants
Non-alcoholic fatty liver disease (NAFLD) is a liver pathology affecting around 25% of the popula... more Non-alcoholic fatty liver disease (NAFLD) is a liver pathology affecting around 25% of the population worldwide. Excess oxidative stress, inflammation and aberrant cellular signaling can lead to this hepatic dysfunction and eventual carcinoma. Molecular hydrogen has been recognized for its selective antioxidant properties and ability to attenuate inflammation and regulate cellular function. We administered hydrogen-rich water (HRW) to 30 subjects with NAFLD in a randomized, double-blinded, placebo-controlled manner for eight weeks. Phenotypically, we observed beneficial trends (p > 0.05) in decreased weight (≈1 kg) and body mass index in the HRW group. HRW was well-tolerated, with no significant changes in liver enzymes and a trend of improved lipid profile and reduced lactate dehydrogenase levels. HRW tended to non-significantly decrease levels of nuclear factor kappa B, heat shock protein 70 and matrix metalloproteinase-9. Interestingly, there was a mild, albeit non-significant...
Cardiovascular Research, 2018
differentiated in cardiogenic, adipogenic and osteogenic directions by addition of specific induc... more differentiated in cardiogenic, adipogenic and osteogenic directions by addition of specific inducers to the cell culture medium. Differentiation efficiency was estimated by qPCR for specific markers of differentiation. Differentiated cells were stained for the specific markers by immunocytochemistry. Results: Peri-infarct cells possessed a higher proliferative potential than the cells from healthy area of the myocardium. They also had a greater propensity to migrate to the area of a "scratch". According to a PCR experiment, the level of activation of specific differentiation markers (TNNT2, BMP2, Runx2 and Fabp4) was higher in peri-infarct cells. Conclusion: Ischemic damage of the myocardium leads to activation of the internal regenerative potential of cardiac stem cells in vivo, which is most pronounced in the peri-infarction zone. P259 Up-regulation of myocardial connexin-43 is involved in compensatory response of the heart to acute injury
Current Pharmaceutical Design, 2021
There are many situations of excessive production of reactive oxygen species (ROS) such as radiat... more There are many situations of excessive production of reactive oxygen species (ROS) such as radiation, ischemia/reperfusion (I/R), and inflammation. ROS contribute to and arises from numerous cellular pathologies, diseases, and aging. ROS can cause direct deleterious effects by damaging proteins, lipids, and nucleic acids as well as exert detrimental effects on several cell signaling pathways. However, ROS are important in many cellular functions. The injurious effect of excessive ROS can hypothetically be mitigated by exogenous antioxidants, but clinically this intervention is often not favorable. In contrast, molecular hydrogen provides a variety of advantages for mitigating oxidative stress due to its unique physical and chemical properties. H2 may be superior to conventional antioxidants, since it can selectively reduce ●OH radicals while preserving important ROS that are otherwise used for normal cellular signaling. Additionally, H2 exerts many biological effects, including anti...
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 2020
Purpose: Metabolic syndrome is associated with several medical risk factors including dyslipidemi... more Purpose: Metabolic syndrome is associated with several medical risk factors including dyslipidemia, hyperglycemia, and obesity, which has become a worldwide pandemic. The sequelae of this condition increase the risk of cardiovascular and neurological disease and increased mortality. Its pathophysiology is associated with redox dysregulation, excessive inflammation, and perturbation of cellular homeostasis. Molecular hydrogen (H 2) may attenuate oxidative stress, improve cellular function, and reduce chronic inflammation. Preclinical and clinical studies have shown promising effects of H 2-rich water (HRW) on specific features of metabolic syndrome, yet the effects of long-term, high-concentration HRW in this prevalent condition remain poorly addressed. Methods: We conducted a randomized, double-blinded, placebo-controlled trial in 60 subjects (30 men and 30 women) with metabolic syndrome. An initial observation period of one week was used to acquire baseline clinical data followed by randomization to either placebo or high-concentration HRW (> 5.5 millimoles of H 2 per day) for 24 weeks. Results: Supplementation with high-concentration HRW significantly reduced blood cholesterol and glucose levels, attenuated serum hemoglobin A1c, and improved biomarkers of inflammation and redox homeostasis as compared to placebo (P < 0.05). Furthermore, H 2 tended to promote a mild reduction in body mass index and waist-to-hip ratio. Conclusion: Our results give further credence that high-concentration HRW might have promising effects as a therapeutic modality for attenuating risk factors of metabolic syndrome.
Physiological Research, 2016
Remote ischemic preconditioning (RIPC) is a novel strategy of protection against ischemia-reperfu... more Remote ischemic preconditioning (RIPC) is a novel strategy of protection against ischemia-reperfusion (IR) injury in the heart (and/or other organs) by brief episodes of non-lethal IR in a distant organ/tissue. Importantly, RIPC can be induced noninvasively by limitation of blood flow in the extremity implying the applicability of this method in clinical situations. RIPC (and its delayed phase) is a form of relatively short-term adaptation to ischemia, similar to ischemic PC, and likely they both share triggering mechanisms, whereas mediators and end-effectors may differ. It is hypothesized that communication between the signals triggered in the remote organs and protection in the target organ may be mediated through substances released from the preconditioned organ and transported via the circulation (humoral pathways), by neural pathways and/or via systemic anti-inflammatory and antiapoptotic response to short ischemic bouts. Identification of molecules involved in RIPC cascades m...
Journal of Hypertension, 2019
After measuring the body mass index, waist circumference and heart rate, the two therapy groups w... more After measuring the body mass index, waist circumference and heart rate, the two therapy groups were confronted, both genders, had not found the statistically signifi cant difference. The results of CHPs (Central Aortic Pressure, End-Systolic Pressure, Mean Arterial Pressure, Pulse Pressure, Augmentation Pressure), Diff-AIx, systolic and diastolic blood pressure during association of ARBs+MRAs therapy compared to ARBs+CCBs, both genders, showed the lowest values with a highly statistically signifi cant difference. Conclusions: These fi ndings provide evidence that ARBs+MRAs treatment reaches best haemodynamic conditions because improve the arterial stiffness (Diff-AIx) and levels of pressures (CHPs) with the intention of giving to arterialventricular coupling an adequate reducing the stress.
Nutrients, 2017
Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaeno... more Omega-3 polyunsaturated fatty acids (PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are permanent subjects of interest in relation to the protection of cardiovascular health and the prevention of the incidence of both ventricular and atrial arrhythmias. The purpose of this updated review is to focus on the novel cellular and molecular effects of omega-3 PUFAs, in the context of the mechanisms and factors involved in the development of cardiac arrhythmias; to provide results of the most recent studies on the omega-3 PUFA anti-arrhythmic efficacy and to discuss the lack of the benefit in relation to omega-3 PUFA status. The evidence is in the favor of omega-3 PUFA acute and long-term treatment, perhaps with mitochondria-targeted antioxidants. However, for a more objective evaluation of the anti-arrhythmic potential of omega-3 PUFAs in clinical trials, it is necessary to monitor the basal pre-interventional omega-3 status of individuals, i.e., red blood cell content, omega-3 index and free plasma levels. In the view of evidence-based medicine, it seems to be crucial to aim to establish new approaches in the prevention of cardiac arrhythmias and associated morbidity and mortality that comes with these conditions.
Bratislavské lekárske listy, 1974
European Heart Journal, 2013
Treatment of hypertension 269 agement studies of its kind resulted in significantly enhanced leve... more Treatment of hypertension 269 agement studies of its kind resulted in significantly enhanced levels of BP control. Applying refined strategies to optimise the potential of this type of intervention (including overcoming prescription resistance) are of clinical importance to optimise BP control.
Canadian Journal of Physiology and Pharmacology, 2018
Uncontrolled production of oxygen and nitrogen radicals results in oxidative and nitrosative stre... more Uncontrolled production of oxygen and nitrogen radicals results in oxidative and nitrosative stresses that impair cellular functions and have been regarded as causative common denominators of many pathological processes. In this review, we report on the beneficial effects of molecular hydrogen in scavenging radicals in an artificial system of•OH formation. As a proof of principle, we also demonstrate that in rat hearts in vivo, administration of molecular hydrogen led to a significant increase in superoxide dismutase as well as pAKT, a cell survival signaling molecule. Irradiation of the rats caused a significant increase in lipid peroxidation, which was mitigated by pre-treatment of the animals with molecular hydrogen. The nuclear factor erythroid 2-related factor 2 is regarded as an important regulator of oxyradical homeostasis, as well as it supports the functional integrity of cells, particularly under conditions of oxidative stress. We suggest that the beneficial effects of mol...
Histochemistry, 1985
Cerium was applied for the ultrastructural, cytochemical localization of adenylate cyclase (EC 4.... more Cerium was applied for the ultrastructural, cytochemical localization of adenylate cyclase (EC 4.6.1.1.). The enzyme activity was stimulated with norepinephrine, prenalterol and cholera toxin in the brown fat cells of newborn rats. The final reaction product was observed in the plasmalemmas of the stimulated adipocytes. The precipitate was finely crystalline, easily visible in the electron microscope and in the X-ray microprobe analysis it yielded cerium and phosphate peaks, respectively. The use of cerium offers a new tool valid for the cytochemical localization of adenylate cyclase enzyme related to the membrane receptors.
Colitis is an inflammatory condition of the bowels associated with abdominal pain, diarrhea, fati... more Colitis is an inflammatory condition of the bowels associated with abdominal pain, diarrhea, fatigue, and fever. Its etiology is multifactorial but related to the overproduction of inflammatory and oxidative mediators. There is currently no cure for this disease, and drugs used to manage it often have deleterious side effects. H2 is recognized as having anti-inflammatory and antioxidant effects, which may qualify it as a novel therapeutic for colitis. We induced an acute model of colitis in mice by administering dextran sulfate sodium (DSS) in drinking water for seven days. Mice were divided into five groups (n=6); normal, colitis, H2-treated colitis, sulfasalazine-treated colitis, and H2 plus sulfasalazine-treated colitis. From days three to ten, mice were given H2, sulfasalazine, or both. H2 was administered via dissolving a hydrogen-generating tablet in water to make hydrogen-rich water (HRW), which was ingested ad libitum and via oral gavage (200 μL). The Disease Activity Index ...
Physiological Research, Sep 15, 2016
Excessive production of oxygen free radicals has been regarded as a causative common denominator ... more Excessive production of oxygen free radicals has been regarded as a causative common denominator of many pathological processes in the animal kingdom. Hydroxyl and nitrosyl radicals represent the major cause of the destruction of biomolecules either by a direct reaction or by triggering a chain reaction of free radicals. Scavenging of free radicals may act preventively or therapeutically. A number of substances that preferentially react with free radicals can serve as scavengers, thus increasing the internal capacity/activity of endogenous antioxidants and protecting cells and tissues against oxidative damage. Molecular hydrogen (H2) reacts with strong oxidants, such as hydroxyl and nitrosyl radicals, in the cells, that enables utilization of its potential for preventive and therapeutic applications. H2 rapidly diffuses into tissues and cells without affecting metabolic redox reactions and signaling reactive species. H2 reduces oxidative stress also by regulating gene expression, and functions as an anti-inflammatory and anti-apoptotic agent. There is a growing body of evidence based on the results of animal experiments and clinical observations that H2 may represent an effective antioxidant for the prevention of oxidative stress-related diseases. Application of molecular hydrogen in situations with excessive production of free radicals, in particular, hydroxyl and nitrosyl radicals is relatively simple and effective, therefore, it deserves special attention.
Journal of Molecular and Cellular Cardiology, 1991
Antioxidants
Cardiac β-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, ... more Cardiac β-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, and fibrosis rendering the heart vulnerable to malignant arrhythmias. We aimed to explore the anti-arrhythmic efficacy of the anti-oxidative and anti-inflammatory compounds, melatonin, and omega-3, and their mechanisms of actions in normotensive and hypertensive rats exposed to isoproterenol (ISO) induced β-adrenergic overdrive. Eight-month-old, male SHR, and Wistar rats were injected during 7 days with ISO (cumulative dose, 118 mg/kg). ISO rats were either untreated or concomitantly treated with melatonin (10 mg/kg/day) or omega-3 (Omacor, 1.68 g/kg/day) until 60 days of ISO withdrawal and compared to non-ISO controls. Findings showed that both melatonin and omega-3 increased threshold current to induce ventricular fibrillation (VF) in ISO rats regardless of the strain. Prolonged treatment with these compounds resulted in significant suppression of ISO-induced extracellular matrix alter...
Antioxidants
The increased production of reactive oxygen species and oxidative stress are important factors co... more The increased production of reactive oxygen species and oxidative stress are important factors contributing to the development of diseases of the cardiovascular and central nervous systems. Molecular hydrogen is recognized as an emerging therapeutic, and its positive effects in the treatment of pathologies have been documented in both experimental and clinical studies. The therapeutic potential of hydrogen is attributed to several major molecular mechanisms. This review focuses on the effects of hydrogen on the cardiovascular and central nervous systems, and summarizes current knowledge about its actions, including the regulation of redox and intracellular signaling, alterations in gene expressions, and modulation of cellular responses (e.g., autophagy, apoptosis, and tissue remodeling). We summarize the functions of hydrogen as a regulator of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated redox signaling and the association of hydrogen with mitochondria as an important...
Biomolecules
MicroRNAs (miRNAs/miRs) such as miR-1, miR-133a, miR-133b, miR-135a, and miR-29b play a key role ... more MicroRNAs (miRNAs/miRs) such as miR-1, miR-133a, miR-133b, miR-135a, and miR-29b play a key role in many cardiac pathological remodeling processes, including apoptosis, fibrosis, and arrhythmias, after a myocardial infarction (MI). Dietary flaxseed has demonstrated a protective effect against an MI. The present study was carried out to test the hypothesis that dietary flaxseed supplementation before and after an MI regulates the expression of above-mentioned miRNAs to produce its cardioprotective effect. Animals were randomized after inducing MI by coronary artery ligation into: (a) sham MI with normal chow, (b) MI with normal chow, and (c–e) MI supplemented with either 10% milled flaxseed, or 4.4% flax oil enriched in alpha-linolenic acid (ALA), or 0.44% flax lignan secoisolariciresinol diglucoside. The feeding protocol consisted of 2 weeks before and 8 weeks after the surgery. Dietary flax oil supplementation selectively upregulated the cardiac expression of miR-133a, miR-135a, an...
International Journal of Molecular Sciences
Reactive oxygen species (ROS) are important molecules in the living organisms as a part of many s... more Reactive oxygen species (ROS) are important molecules in the living organisms as a part of many signaling pathways. However, if overproduced, they also play a significant role in the development of cardiovascular diseases, such as arrhythmia, cardiomyopathy, ischemia/reperfusion injury (e.g., myocardial infarction and heart transplantation), and heart failure. As a result of oxidative stress action, apoptosis, hypertrophy, and fibrosis may occur. MicroRNAs (miRNAs) represent important endogenous nucleotides that regulate many biological processes, including those involved in heart damage caused by oxidative stress. Oxidative stress can alter the expression level of many miRNAs. These changes in miRNA expression occur mainly via modulation of nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuins, calcineurin/nuclear factor of activated T cell (NFAT), or nuclear factor kappa B (NF-κB) pathways. Up until now, several circulating miRNAs have been reported to be potential biomarke...