We recently reported that in vitro Cognac polyphenolic compounds (CPC) induce NO-dependent vasorelaxant effects and stimulate cardiac function. In the present study, we aim to investigate the effect of CPC on both nitric oxide (NO) and superoxide anions (O2-) production in cultured human endothelial cells. In addition, its effect on the bradykinin (BK)-induced NO production was also tested. The role and sources of O2- in the concomitant effect of BK plus CPC were pharmacologically determined. NO and O2- signals were measured using electron paramagnetic resonance technique using specific spin trappings. Both, CPC and BK induced an in crease in NO production in human endothelial cells. The combination of both further enhanced NO release. The capacity of CPC plus BK to increase NO signal was blunted by the NO synthase inhibitor, NG-nitro-L-arginine methyl ester, and was enhanced in the presence either of superoxide dismutase or catalase. Moreover, CPC plus BK response was greater after inhibition of either NADPH oxidase by apocynin or xanthine oxidase by allopurinol but it was not affected by rotenone. CPC did not affect O2- level either alone or after its increase upon lipopolysaccharide treatment. Finally, the capacity of BK alone to increase NO was enhanced either by apocynin or allopurinol. Altogether, these data demonstrate that CPC is able to directly increase NO production without affecting O2- and enhances the BK-induced NO production in human endothelial cells. The data highlight the ability of BK to stimulate not only NADPH oxidase- but also xanthine oxidase-inhibitor sensitive mechanisms that reduce its efficiency in increasing NO either alone or in the presence of CPC. These results bring pharmacological evidence for vascular protection by CPC via its potentiating effect of BK response in terms of endothelial NO release., A. Sall Diallo, M. Sarr, H. A. Mostefai, N. Carusio, M. Pricci, R. Andriantsitohaina., and Obsahuje bibliografii a bibliografické odkazy
Flavin7 (F7) is a nutritional supplement often taken by cancer patients in Central Europe during chemo- and radiation therapy. In this study, investigation of the antiproliferative and antiangiogenic activities of this supplement were performed. Flavin7 showed antiprolif erative activity in Jurkat as well as in HeLa cells. It significantly reduced the growth of both cancer cell lines at the doses of 200 μg/ml to 20 μg/ml (p<0.001 and p<0.01, respectively). In F7-treated Jurkat cells we found a significant increase in the fraction of cells with sub-G0/G1 DNA content, which is considered to be a marker of apoptotic cell death. Apoptosis was also confirmed by annexin V staining and DNA fragmentation. Furthermore, F7 at the doses of 100 μg/ml to 4 μg/ml inhibited endothelial cell migration and capillary tube formation what indicates its potential antiangiogenic properties. Flavin7 also inhibited the activity of matrix metalloproteinases (MMPs), preferentially MM P-9, at the doses of 100 μg/ml to 4 μg/ml. Our data suggest that F7 possesses marked antiproliferative and antiangiogenic properties in vitro. Further research is needed to elucidate also its in vivo activities., J. Mojžiš, M. Šarišský, M. Pilátová, V. Voharová, L. Varinská, G. Mojžišová, A. Ostro, P. Urdzík, R. Dankovčik, L. Mirossay., and Obsahuje bibliografii a bibliografické odkazy
This study sought to evaluate whether consumption of polyphenol extract from Cognac (CPC) modulates platelet activation and cardiovascular reactivity in rats. Male Wistar rats were treated daily for 4 weeks by intra-gastric gavage receiving CPC at 80 mg/kg/day or vehicle (5 % glucose). Platelet adhesion and aggregation in response to different activators were assessed. Cardiac and vascular reactivity in response to various agonists as well as NO measurement by electron paramagnetic resonance technique were investigated in isolated heart and thoracic aorta. Oral administration of CPC decreased platelet aggregation induced by ADP but not by collagen. CPC did not affect adhesion to collagen. The chronotropic but not the inotropic response to isoprenaline was reduced without alteration of NO production in hearts from CPC-treated rats. CPC treatment did not affect ex vivo relaxation to acetylcholine nor NO content of rat aorta. CPC did not significantly alter the response to phenylephrine in aorta despite the participation of endothelial vasoconstrictor products. In summary, chronic treatment with CPC has no impact on ex vivo vascular and cardiac reactivity; however, it reduced heart work and platelet aggregation. These data suggest the existence of compounds in Cognac that may decrease the risk of coronary thrombosis and protect against some cardiac diseases., N. Carusio, R. Wangensteen, A. Filippelli, R. Andriantsitohaina., and Obsahuje bibliiografii a bibliografické odkazy
Oxidative stress is a phenomenon associated with imbalance between production of free radicals and reactive metabolites (e.g. superoxide and hydrogen peroxide) and the antioxidant defences. Oxidative stress in individuals with Down syndrome (DS) has been associated with trisomy of the 21st chromosome resulting in DS phenotype as well as with various morphological abnormalities, immune disorders, intellectual disability, premature aging and other biochemical abnormalities. Trisomy 21 in patients with DS results in increased activity of an important antioxidant enzyme Cu/Zn superoxide dismutase (SOD) which gene is located on the 21st chromosome along with other proteins such as transcription factor Ets-2, stress inducing factors (DSCR1) and precursor of beta-amyloid protein responsible for the formation of amyloid plaques in Alzheimer disease. Mentioned proteins are involved in the management of mitochondrial function, thereby promoting mitochondrial theory of aging also in people with DS. In defence against toxic effects of free radicals and their metabolites organism has built antioxidant defence systems. Their lack and reduced function increases oxidative stress resulting in disruption of the structure of important biomolecules, such as proteins, lipids and nucleic acids. This leads to their dysfunctions affecting pathophysiology of organs and the whole organism. This paper examines the impact of antioxidant interventions as well as positive effect of physical exercise on cognitive and learning disabilities of individuals with DS. Potential terapeutic targets on the molecular level (oxidative stress markers, gene for DYRK1A, neutrophic factor BDNF) after intervention of natural polyphenols are also discussed., J. Muchová, I Žitňanová, Z. Ďuračková., and Obsahuje bibliografii
Increased amount of collagen type I and decreased amount of type III is described in various pathological processes in the vascular wall. Polyphenols were shown to have protective effect on endothelium, decrease blood pressure and prevent oxidative damage induced by various stimuli. Tetrachlormethane (CCl4) is a toxic substance with known negative systemic effects induced by free radicals. Chronic administration of CCl4 for 12 weeks led to an increase of collagen type I and a decrease of type III in the wall of aorta. Parallel administration of red wine polyphenols significantly reduced the increase of collagen type I, at the same time the content of type III rose to the level above controls. After 4 weeks of spontaneous recovery no changes were observed. If polyphenols were administered during the recovery period, there was a decrease of type I and an increase of type III collagen content in the aorta. It can be concluded that polyphenols have a tendency to lower the amount of type I and to increase the proportion of type III collagen in the wall of the aorta. These changes are significant in prevention or in regression of changes induced by chronic oxidative stress. This effect of polyphenols is most likely the result of their influence on MMP-1 and TIMP activities through which they positively influence the collagen types I and III content ratio in the vascular wall in favor of the type III collagen., L. Hlavačková ... [et al.]., and Obsahuje seznam literatury