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1

Endotoxaemia in rats: role of leucocyte sequestration in rapid pulmonary nitric oxide synthase-2 expression

100%

Gebska A., Olszanecki R., Korbut R.

Journal of Physiology and Pharmacology

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2005

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tom 56

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nr 2

Nitric oxide (NO), depending on the amount, time and source of generation may exert both, protective and deleterious actions during endotoxic acute lung injury (ALI). Evaluation of the expression and localization of NOS isoforms in the lung of lipopolysaccharide (LPS) - treated rats may contribute to understanding the role of NO in pathogenesis of ALI. Tissue samples (lung, heart, liver, kidney and spleen) as well as peripheral blood polymorphonuclear cells (PMNs) were collected from control male Wistar rats and LPS - treated animals, 15, 30, 60, 120 and 180 min after LPS injection (2 mg kg-1 min-1 for 10 minutes, i.v.). Levels of NOS-2 and NOS-3 mRNA and protein in tissues and PMNs were estimated by RT-PCR, Northern blotting and Western blotting. Additionally, myeloperoxidase (MPO) activity in tissue samples was assayed. NOS-3 mRNA as well as protein were detected in lungs of control animals; pulmonary NOS-3 expression was not influenced by LPS. The induction of NOS-2 mRNA in rat lungs and in PMNs isolated from peripheral blood was observed 15 minutes after LPS challenge. In contrast, increase of NOS-2 mRNA in the heart, kidneys, liver and spleen was observed 2-3 hours after LPS injection. In all tissues rise in NOS-2 mRNA was followed after 1-2 hours by increase of NOS-2 protein. Importantly, progressive leukocyte sequestration in the lung parenchyma that started as early as 15 min after LPS injection was revealed only in the lungs; in other organs no significant changes in MPO activity were detected up to 180 min after LPS injection. In conclusion, infusion of LPS caused much more rapid expression of NOS-2 in lungs as compared to the heart, kidneys, liver and spleen. Early induction of NOS-2 may depend on the LPS-stimulated rapid neutrophil sequestration within lung vasculature and fast induction of NOS-2 in sequestrated neutrophils.

2

Production of prostacyclin and prostaglandin E2 in resting and IL-1beta-stimulated A549, HUVEC and hybrid EA.HY 926 cells

100%

Olszanecki R., Gebska A., Korbut R.

Journal of Physiology and Pharmacology

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2006

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tom 57

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nr 4

Production of arachidonic acid (AA) metabolites - prostacyclin (PGI2) in large vessels and prostaglandin E2 (PGE2) in microcirculation is intrinsically involved in maintenance of vascular wall homeostasis. EA.hy 926 is a hybrid cell line, is derived by fusion of HUVEC with A549 cells. The aim of this study was to examine the production of prostacyclin and PGE2 in resting and IL-1ß-stimulated EA.ha 926 cells, in comparison with its progenitor cells. Non-stimulated EA.hy 926 cells has been found to produce much lower amounts of prostacyclin than resting HUVEC. Resting hybrid cells produced more PGE2 than prostacyclin, despite they expressed high levels of COX-1 and PGI2 synthase. On the contrary to HUVEC and A549, EA.hy 926 cells did not respond to IL-1ß with COX-2 induction and increase of prostaglandin production, however they did it in response to lysophosphatidylcholine (LPC). The characteristics of EA.hy 926 cells in terms of the pattern of prostanoid formation could facilitate studies on endothelial metabolism and role of these important lipid mediators.

3

Flavonoids and nitric oxide synthase

100%

Olszanecki R., Gebska A., Kozlovski V. I., Gryglewski R. J.

Journal of Physiology and Pharmacology

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2002

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tom 53

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nr 4,1

Induction of NOS-2 in macrophages and smooth muscles within vascular wall with concomittant suppression of endothelial NOS-3 activity is considered to be a hallmark of vascular inflammation that triggers atherogenesis. Accordingly, drugs designed to reverse these changes should not only support vaning function of NOS-3 but also suppress proinflammatory NO production by NOS-2. It means that using selective inhibitors of induction of NOS-2 (they spare ex definitione constitutive activity of NOS-3) is a more rational approach than using isselectivel. inhibitors of activity of previously induced NOS-2. First of all, those drugs are never sufficiently selective. In our work we tried to identify inhibitors of NOS-2 induction within the group of flavonoids, known stimulators of NOS-3 with putative antiatherogenic effects. Representatives of four main groups of flavonoids: flavonols (kaempferol, quercetin, rutin), flavones (apigenin, primuletin), flavanols (catechine) and flavanones (hesperetin, hesperidin, naringenin) were tried on NOS-2 induction and activity in the in vitro model of LPS-treated macrophages (cell line J774.2). While none of these compounds inhibited activity of NOS-2, all with unexpectedly scattered potencies inhibited induction of NOS-2 protein in LPS-treated J774.2 cells, as evidenced by Western blotting technique. Subsequently, RT-PCR and Northern blotting methods revealed that so far the most potent compounds, kaempferol and apigenin, at micromolar concentrations did inhibit NOS-2 induction at the level of NOS-2 gene transcription. We conclude that some of flavonoids are potent inhibitors of NOS-2 induction. At the same time they may increase endothelial NOS-3 activity. Could these flavonoids become natural parents of future drugs, which will be used for reversal of inflammatory component of atherothrombosis?

4

Inhibition of NOS-2 induction in LPS-stimulated J774.2 cells by 1,5-isoquinolinediol, an inhibitor of PARP

88%

Olszanecki R., Gebska A., Jawien J., Jakubowski A., Korbut R.

Journal of Physiology and Pharmacology

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2006

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tom 57

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nr 1

Activation of both poly (ADP-ribose) polymerase (PARP) and inducible nitric oxide synthase (NOS-2) have been implicated in the pathogenesis of various forms of inflammation, therefore compounds which may simultaneously inhibit both pathways are of potential therapeutic interest. We tested the influence of potent inhibitor of PARP, 1, 5-isoquinolinediol (ISO), on NOS-2 induction in model of mouse macrophages (cell line J774.2) stimulated with lipopolysaccharide (1 µg/ml). Pretreatment with ISO (1-300 µM) resulted in dose-dependent inhibition of accumulation of NOS-2-derived nitrite in culture medium (IC50 = 9,3 µM) as well as inhibition of NOS-2 protein induction in cultured J774.2 cells; ISO given 10 hours after LPS did not influence activity of NOS-2. Interestingly, another PARP inhibitor, 3-aminobenzamide (3-AB, 10-3000 µM), did not influence 24-hr nitrite accumulation in J774.2 cell culture, either administered 15 minutes prior to LPS or 10 hrs after LPS. Scavenging of reactive oxygen species by use of mixture of SOD and catalase (SOD/Cat, 100/300 - 1000/3000 U/ml) as well as cell permeable SOD-mimetic [Mn(III)TBAP, 1- 100 µM], did not influence NOS-2 induction in J774.2 cells. In summary, we identified 1, 5-isoquinoline as potent inhibitor of induction of NOS-2 in LPS-treated mouse macrophages. The exact mechanism of inhibitory action of this compound on NOS-2 induction requires further investigation.

5

Występowanie różnych gatunków gronkowców w jamie ustnej człowieka

76%

Kwapisz E., Wierzbowska M., Garbacz K., Krause M., Gebska A., Ziolkowska-Klinkosz M.

Postępy Mikrobiologii. Suplement

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2017

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tom 56

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nr 2

6

Angiotensin metabolism in rat stomach wall: prevalence of angiotensin-(1-7) formation

76%

Olszanecki R., Madej J., Suski M., Gebska A., Bujak-Gizycka B., Korbut R.

Journal of Physiology and Pharmacology

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2009

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tom 60

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nr 1

191-196

Our view of renin-angiotensin system (RAS) has changed over the past two decades: new metabolites and pathways have been described; also the importance of local renin-angiotensin systems became more clearly understood. However, there is relatively scarce information about formation and action of angiotensin peptides in gastrointestinal tract, especially in the stomach. Here, using LC-ESI-MS method we assessed the metabolism of Ang I in organ bath of rat stomach wall. Additionally we compared the expression of mRNA of angiotensin converting enzymes (ACE, ACE2) and neprilysin (NEP) in the stomach, aorta and renal artery in rats. Despite, similar levels of expression of ACE and ACE2 mRNA in stomach wall, aorta and renal artery, the absolute amounts of main Ang I metabolites produced by stomach wall (in ng/mg of dry tissue) were much lower than that produced by aorta and renal artery. Also, the pattern of angiotensin I metabolites was different: opposite to aorta and renal artery, incubation of Ang I with stomach wall fragments resulted in predominant formation of Ang-(1-7) and relatively lower production of Ang II. In stomach wall both, perindoprilat and tiorphan decreased production of Ang II, but did not influence generation of Ang-(1-7). In conclusion, we identified Ang-(1-7) as the main product of Ang I conversion in rat stomach wall. The biological role of prevalence of Ang-(1-7) formation in stomach require further investigation.

7

Metabolism of bradykinin in aorta of hypertensive rats

76%

Bujak-Gizycka B., Olszanecki R., Madej J., Suski M., Gebska A., Korbut R.

Acta Biochimica Polonica

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2011

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tom 58

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nr 2

Alterations in the formation and metabolism of bradykinin (Bk) are hypothesized to play a role in the pathophysiology of hypertension, atherosclerosis and vascular complications of diabetes. However, despite its prominent role in cardiovascular regulation, studies on bradykinin have been limited by various difficulties in accurate measurements of this peptide in biological samples. In this study, using the LC-ESI-MS method we estimated the conversion of exogenous Bk to its main metabolites - Bk-(1-5) and Bk-(1-7) - in endothelial cell culture and in fragments of aorta of normotensive (WKY) and hypertensive rats (SHR). The effects of angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) inhibitors were more pronounced in SHR: perindoprilat inhibited Bk-(1-5) formation by 49 % and 76 % in WKY and SHR rats, respectively, and tiorphan tended to decrease formation of Bk-(1-5) in both groups of animals. The degradation of bradykinin and generation of both metabolites were significantly higher in the aorta of SHR rats than in WKY controls. Our results show that even in relatively early hypertension (in 4-month old SHR rats) inactivation of Bk by aorta wall is enhanced.

8

The influence of angiotensin-(1-7) peptidomimetic (AVE 0991) and nebivolol on angiotensin i metabolism in aorta of apoE-knockout mice

64%

Olszanecki R., Suski M., Gebska A., Toton-Zuranska J., Kus K., Madej J., Bujak-Gizycka B., Jawien J., Korbut R.

Journal of Physiology and Pharmacology

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2013

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tom 64

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nr 3

9

Effect of curcumin on atherosclerosis in apoE-LDLR - double knockout mice

64%

Olszanecki R., Jawien J., Gajda M., Mateuszuk L., Gebska A., Korabiowska M., Chlopicki S., Korbut R.

Journal of Physiology and Pharmacology

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2005

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tom 56

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nr 4

It is widely appreciated that inflammation and oxidant stress contribute to atherogenesis. Curcumin, a polyphenolic natural compound has been reported to possess anti-inflammatory and anti-oxidant actions. We hypothesized that curcumin could inhibit the development of atherosclerosis in the apoE/LDLR - double knockout mice fed with Western diet (21% fat, 0.15% cholesterol w/w, without cholic acid). Curcumin (purity 98%), premixed with diet, was given for 4 months at a dose of 0.3 mg/per day/per mouse. In this model curcumin inhibited atherogenesis, measured both by "en face" method (25,15±2,9% vs. 19,2±0,6%, p<0,05) and "cross-section" method (565867±39764 µm2 vs. 299201±20373 µm2, p<0,05). Importantly, curcumin influenced neither the concentrations of cholesterol and triglycerides in blood nor animal body weight. To our knowledge, this is the first report that shows the anti-atherogenic effect of low dose of curcumin in fine model of atherosclerosis: gene-targeted apoE/LDLR - double knockout mice.

10

Angiotensin-(1-7) receptor Mas agonist ameliorates progress of atherosclerosis in apoE-knockout mice

52%

Jawien J., Toton-Zuranska J., Gajda M., Niepsuj A., Gebska A., Kus K., Suski M., Pyka-Fosciak G., Nowak B., Guzik T. J., Marcinkiewicz J., Olszanecki R., Korbut R.

Journal of Physiology and Pharmacology

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2012

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tom 63

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nr 1

Ograniczanie wyników

Endotoxaemia in rats: role of leucocyte sequestration in rapid pulmonary nitric oxide synthase-2 expression

Production of prostacyclin and prostaglandin E2 in resting and IL-1beta-stimulated A549, HUVEC and hybrid EA.HY 926 cells

Flavonoids and nitric oxide synthase

Inhibition of NOS-2 induction in LPS-stimulated J774.2 cells by 1,5-isoquinolinediol, an inhibitor of PARP

Występowanie różnych gatunków gronkowców w jamie ustnej człowieka

Angiotensin metabolism in rat stomach wall: prevalence of angiotensin-(1-7) formation

Metabolism of bradykinin in aorta of hypertensive rats

The influence of angiotensin-(1-7) peptidomimetic (AVE 0991) and nebivolol on angiotensin i metabolism in aorta of apoE-knockout mice

Effect of curcumin on atherosclerosis in apoE-LDLR - double knockout mice

Angiotensin-(1-7) receptor Mas agonist ameliorates progress of atherosclerosis in apoE-knockout mice