Gap junction connexin channels are important determinants of myocardial conduction and synchronization that is crucial for coordinated heart function. One of the main risk factors for cardiovascular events that results in heart attack, congestive heart failure, stroke as well as sudden arrhythmic death is hypertension. Mislocalization and/or dysfunction of specific connexin-43 channels due to hypertension-induced myocardial remodeling have been implicated in the occurrence of lifethreatening arrhythmias and heart failure in both, humans as well as experimental animals. Recent studies suggest that downregulation of myocardial connexin-43, its abnormal distribution and/or phosphorylation might be implicated in this process. On the other hand, treatment of hypertensive animals with cardioprotective drugs (e.g. statins) or supplementation with non-pharmacological compounds, such as melatonin, omega-3 fatty acids and red palm oil protects from lethal arrhythmias. The antiarrhythmic effects are attributed to the attenuation of myocardial connexin-43 abnormalities associated with preservation of myocardial architecture and improvement of cardiac conduction. Findings uncover novel mechanisms of cardioprotective (antihypertensive and antiarrhythmic) effects of compounds that are used in clinical settings. Well-designed trials are needed to explore the antiarrhythmic potential of these compounds in patients suffering from hypertension., T. Egan Benova, B. Szeiffova Bacova, C. Viczenczova, E. Diez, M. Barancik, N. Tribulova., and Obsahuje bibliografii
It is unknown whether the longer duration of vibration training (VT) has a beneficial effect on Parkinson's disease (PD). And also, the mechanisms underlying the reported sensorimotorimprovement in PD induced by short-duration of VT has not been determined. Here, we investigated the effects of longer duration (4 weeks) of low amplitude vibration (LAV) training on the numbers of dopaminergic neurons in the substantia nigra by immunostaining and the levels of dopamine (DA) and brainderived neurotrophic factor (BDNF) in the striatum by HPLC and ELISA in the chronic MPTP lesion mouse. We demonstrated for the first time that the longer duration of VT could significantly increase the numbers of nigrostriatal DA neurons and the contents of striatal DA and BDNF in the MPTP mice. Our findings implied that longer duration of VT could protect dopaminergic neurons from the MPTP-induced damage probably by upregulating BDNF and also provided evidence for the beneficial effect of longer duration of VT on PD at the cellular and molecular level., L. Zhao, L. X. He, S. N. Huang, L. J. Gong, L. Li, Y. Y. Lv, Z. M. Qian., and Obsahuje bibliografii
Chronic kidney disease (CKD) represents a serious public health problem with increasing prevalence and novel approaches to renal protection are continuously under investigation. The aim of this study was to compare the effect of melatonin and angiotensin II type 2 receptor agonist compound 21 (C21) to angiotensin converting enzyme inhibitor captopril and angiotensin II type 1 receptor blocker olmesartan on animal model of doxorubicin nephrotoxicity. Six groups of 3-month-old male Wistar rats (12 per group) were treated for four weeks. The first group served as a control. The remaining groups were injected with a single dose of doxorubicin (5 mg/kg i.v.) at the same day as administration of either vehicle or captopril (100 mg/kg/day) or olmesartan (10 mg/kg/day) or melatonin (10 mg/kg/day) or C21 (0.3 mg/kg/day) was initiated. After four week treatment, the blood pressure and the level of oxidative stress were enhanced along with reduced glomerular density and increased glomerular size. Captopril, olmesartan and melatonin prevented the doxorubicin-induced increase in systolic blood pressure. All four substances significantly diminished the level of oxidative burden and prevented the reduction of glomerular density and modestly prevented the increase of glomerular size. We conclude that captopril, olmesartan, melatonin and C21 exerted a similar level of renoprotective effects in doxorubicin-induced nephrotoxicity., J. Hrenák ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Acute renal failure (ARF) is mainly characterized by acute tubular necrosis. No significant change was found for mortality rates over the past few decades despite significant advances in supportive care. In recent years, great effort has been focused on traditional and herbal medicine, which is much less toxic than those agents conventionally used and which is nowadays considered as a novel therapeutic agent for ARF. However, the effect of ginsenosides (GS) administered orally on ARF has not been reported yet and little is known about its cellular and molecular mechanism. The purpose of the study is to investigate the protective effect of ginsenoside in rats with ARF on the changes of tyrosine hydroxylase immunoreactivity (TH-IR) as well as on the involvement of mitogen-activated protein kinases (MAPK) in the locus coeruleus. In our assay, glycerol-induced acute renal failure in rats was employed to study the protective effects of ginsenoside. Our results indicated that the treatment of ARF rats with ginsenosides for 48 h significantly reduced the serum blood urea nitrogen, creatinine level, and lipid peroxidation, restored the GSH level and the normal renal morphology. Immunohistochemistry showed that an obvious increase of TH-IR was further enhanced in ARF+GS group. The same effect was also observed in the changes of p-ERK1/2-IR in the locus coeruleus. Our results suggest that ginsenoside administered orally may have a strong renal protective effect against glycerol-induced ARF, and ginsenoside can also activate the brain catecholaminergic neurons in the locus coeruleus. Our future attention will be focused to the question whether there is a correlation between the renal protective effect of ginsenosides against acute renal failure and the activation of tyrosine hydroxylase in the locus coeruleus., H. A. Zhang ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Generation of reactive oxygen species significantly contributes to the pathogenesis of acute renal failure (ARF) induced by myoglobin release. Ginsenosides (GS), the principal active ingredients of ginseng, is considered as an extremely good antioxidative composition of Chinese traditional and herbal drugs. The purpose of the present study was to investigate the protective effect of ginsenoside in rats with ARF on the changes of cholinergic nervous system in the kidney as well as on the involvement of mitogen-activated protein kinases (MAPK) in the hypothalamic paraventricular nuclei (PVN). In our assay, glycerolinduced acute renal failure in rats was employed to study the protective effects of ginsenoside. Our results indicated that the treatment of ARF rats with ginsenosides for 48 h significantly reduced lipid peroxidation, restored the superoxide dismutase (SOD) level. Meanwhile, the obvious increase of choline acetyltransferase-immunoreactivity (ChAT-IR) in the proximal convoluted tubular cells (PCT) was observed by immunohistochemistry in ARF+GS group. The same effect was also observed in the changes of p-ERK1/2-IR in the hypothalamic paraventricular nuclei. Our results suggest that ginsenoside administered orally may have a strong renal protective effect against glycerol-induced ARF, reduce the renal oxidative stress, and ginsenoside can also activate the cholinergic system in PCT, simultaneously MAPK signal pathway in the PVN was also activated., J. Zhou, H. A. Zhang, Y. Lin, H. M. Liu, Y. M. Cui, Y. Xu, N. Zhao, J. M. Ma, K. Fan, C. L. Jiang., and Obsahuje bibliografii
This study was designed to determine the gastroprotective properties of quercetin in ischemia/reperfusion-induced gastric mucosal injury and the involvement of endogenous prostaglandins in this process. Oral pretreatment of rats with quercetin (100 mg.kg-1) 30 min before surgery significantly decreased the length of gastric mucosal lesions. However, lower doses of quercetin (25 and 50 mg.kg-1) only slightly decreased the gastric mucosal injury. Intraperitoneal application of indomethacin (5 mg.kg-1) had no effect in control (sham-operated) animals, but significantly worsened gastric injury in non-treated animals after ischemia/reperfusion. Furthermore, indomethacin only slightly reversed protective effect of quercetin. Non-treated animals showed a marked decrease in adherent mucus after ischemia/reperfusion. On the other hand, application of quercetin prevented this significant decrease even in animals pretreated with indomethacin. It can be concluded that antioxidant properties of quercetin and its mucus protective effect might be the main factors responsible for its protective effect against ischemia/reperfusion-induced gastric mucosal injury., J. Mojžiš, K. Hviščová, D. Germanová, D. Bukovičová, L. Mirossay., and Obsahuje bibliografii
Reactive oxygen species can be generated by daily exposure of the skin to ultraviolet light and may cause some subchronic and chronic skin disorders. The aim of this study was to investigate a possible preventive role of a-tocopherol acetate (ATA) on ultraviolet B (UVB) induced peroxidation by assessing lipid peroxide (LPO) levels and activity of reactive oxygen scavenging enzymes including glutathione peroxidase and superoxide dismutase (SOD) in guinea pigs. ATA was topically applied to the skin for three weeks before a single dose of 0.9 J/cm2 UVB irradiation on the skin and lipid peroxide levels and antioxidants in plasma, skin and liver and erythrocytes were determined after decapitation. Topical application of ATA prevented the UVB irradiation-induced reduction of scavenging enzyme activities in skin and erythrocytes. In conclusion, we suggest that topical applications of ATA before UVB irradiation is effective in protecting the skin from unwanted effects of UVB irradiation., Y. Saral, B. Uyar, A. Ayar, M. Naziroglu, S. Yilmaz., and Obsahuje bibliografii
The effects of acute exposure to cadmium (Cd) on the blood antioxidant defense system, lipid peroxide concentration and hematological parameters, as well as the possible protective role of vitamin E were studied. Male Wistar albino rats (3 months old) were treated with cadmium (0.4 mg Cd/kg b.m., i.p., 24 h before the experiment) or with vitamin E + Cd (20 IU Vit E/kg b.m., i.m., 48 h + 0.4 mg Cd/kg b.m., i.p., 24 h before the experiment). The hematological parameters were assessed: red blood cell counts, hematocrit value and hemoglobin concentration were significantly decreased in the blood of Cd-treated rats. Intoxication with cadmium was also followed by significantly increased lipid peroxide concentrations. We also observed increased activity of antioxidant defense enzymes: copper zinc containing superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase as well as concentrations of non-enzymatic components of antioxidant defense system: reduced glutathione, vitamin C and vitamin E. Pretreatment with vitamin E exhibited a protective role on the toxic effects of cadmium on the hematological values, lipid peroxide concentration as well as on enzymatic and non-enzymatic components of antioxidant defense system., B. I. Ognjanović, S. Z. Pavlović, S. D. Maletić, R. V. Žikić, A. Š. Štajn, R. M. Radojičić, Z. S. Saičić, V. M. Petrović., and Obsahuje bibliografii
Understanding the behavior of single proteins at the polyelectrolyte multilayer film/solution interface is of prime importance for the designing of bio-functionalized surface coatings. In the present paper, we study the adsorption of the model proteins, albumin and lysozyme, as well as basic fibroblast growth factor (FGF-2) on a polysaccharide multilayer film composed of quaternized chitosan and heparin. Several analytical methods were used to describe the formation of the polysaccharide film and its interactions with the proteins. Both albumin and lysozyme adsorbed on quaternized chitosan/heparin films, however this process strongly depended on the terminating polysaccharide. Protein adsorption was driven mainly by electrostatic interactions between protein and the terminal layer of the film. The effective binding of FGF-2 by the heparinterminated film suggested that other interactions could also contribute to the adsorption process. We believe that this FGF-2- presenting polysaccharide film may serve as a biofunctional surface coating for biologically-related applications., M. Kumorek, D. Kubies, T. Riedel., and Obsahuje bibliografii
a1_Proteinase-activated receptor-2 (PAR-2) is a ubiquitous surface molecule participating in many biological processes. It belongs to the family of G protein-coupled receptors activated by the site-specific proteolysis of trypsin and similar proteases. Altered function of PAR-2 has been described in different malignant tumors. In the present study, we investigated the expression of PAR-2 in breast cancer surgical specimens and the role of trypsin in breast cancer cell line MDA MB-231 proliferation and metabolism. A total of 40 surgical samples of infiltrative ductal breast cancer and breast cancer cell line were included in this study. We analyzed PAR-2 expression by immunohistochemistry, RT-PCR and western blot. Activation of PAR-2 on cell line MDA MB-231 was measured using calcium mobilization assay determined by flow cytometry. MTT cell metabolism assay and cell count analysis were used to assess the trypsin influence on breast cancer cell line MDA MB-231 proliferation. Immunohistochemical examination showed the expression of PAR-2 in all samples of breast cancer surgical specimens and high levels of cell lines which was confirmed by RT-PCR and western blot., a2_Calcium mobilization assay corroborated the activation of PAR-2 on cell line MDA MB-231 either by trypsin or by an agonistic peptide. Cell metabolism assay and cell count analysis showed significant differences of proliferative activity of breast cancer cells dependent on the presence or absence of trypsin and serum in the culture medium. PAR-2 is expressed by high levels in infiltrative ductal breast cancer tissue specimens. PAR-2 is also strongly expressed in studied breast cancer cell lines. PAR-2 is activated by trypsin and also by agonistic peptide in the model of breast cancer cell line MDA MB-231. Activation of PAR-2 in vitro influences proliferative and metabolic activity of breast cancer cell line MDA MB-231. The action of trypsin is modified by the presence of serum which is a potential source of protease inhibitors., R. Matěj, P. Manďáková, I. Netíková, P. Poučková, T. Olejár., and Obsahuje biblografii a bibliografické odkazy