Wyniki wyszukiwania

1

Transcriptional upregulation of gastrin in response to peroxisome proliferator-activated receptor gamma agonist triggers cell survival pathways

100%

Ptak-Belowska A., Pawlik M. W., Krzysiek-Maczka G., Brzozowski T., Pawlik W. W.

Journal of Physiology and Pharmacology

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2007

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tom 58

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nr 4

Peroxisome proliferator-activated receptor (PPAR ) are members of the largest nuclear hormone receptor family of transcription factors (1). PPAR gamma (PPAR) plays an important role in adipogenesis, control of sensitivity to insulin, inflammation and atherosclerosis but recent studies also suggest that PPAR is involved in cell cycle withdrawal. PPAR can promote cell differentiation, exert an antiproliferative action and inhibit angiogenesis (2, 3). However, there are studies showing that activation of PPAR promotes the development of colon cancer (4). These data are in sharp contrast with studies that attribute anticancer effects to PPAR in gastrointestinal malignancies. Probably, the action of PPAR on cell cycle and proliferation depends on the cell type and presence of other stimuli that predispose cells to cancer development. Amidated and non-amidated gastrins may play an important role in the proliferation and carcinogenesis of GI cancers. It is known that gastrin peptides activate phosphorylation of Protein Kinase B (PKB/Akt) and anti-apoptotic signalling but there is little known about the link between gastrins and PPAR receptors in relation to apoptosis.

2

Involvement of central and peripheral histamine H3 receptors in the control of the vascular tone and oxygen uptake in the mesenteric circulation of the rat

100%

Obuchowicz R., Pawlik M. W., Brzozowski T., Konturek S. J., Pawlik W. W.

Journal of Physiology and Pharmacology

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2004

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tom 55

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nr 1,2

Data concerning cardiovascular effects of peripherally and centrally located histamine H3 receptor stimulation are contradictory, and despite excessive studies their role in the control of the cardiovascular function have not been cleared yet. Effect of histamine H3 receptors activation have been attributed to modulation of sympathetic system activity but exact role of peripherally and centrally located histamine H3 receptors stimulation in the modulation of vascular tone of the mesentery and intestinal metabolism remains unexplored. Aim of the present study was to evaluate the role of centrally and peripherally located histamine H3 receptors in the modulation of vascular tone of the mesentery and metabolic activity of intestinal tissue. In anesthetized rats total mesenteric blood flow (MBF), mucosal intestinal blood flow (LDBF), intestinal oxygen uptake (VO2) and arterial pressure (AP) were determined. Intestinal arterial conductance (C) was also calculated. Administration of the selective histamine H3 receptor agonist imetit (10 µmol/kg i.a) evoked marked changes in hemodynamic and metabolic parameters; MBF, LDBF, C and VO2 were significantly increased, whereas AP was significantly decreased. Pretreatment with histamine H3 receptor antagonist clobenpropit (4 µmol/kg i.a.) abolished imetit-induced circulatory and oxygen uptake responses. Clobenpropit (4 µmol/kg i.a.) alone failed to affect the MBF, LDBF, AP, C and VO2 values. Central administration of imetit (0.1 µmol i.c.v.) markedly increased AP and decreased MBF, LDBF, C and VO2. Pretreatment with histamine H3 receptor antagonist clobenpropit (0,4 µmol i.c.v.) diminished circulatory and metabolic responses to centrally injected imetit. Central histamine H3 receptors blockade by clobenpropit evoked no significant changes in the mesenteric arterial and mucosal microcirculatory blood flow, intestinal metabolism and mean arterial pressure. We conclude that, peripheral histamine H3 receptors when stimulated decreases vasoconstrictory tone of the mesenteric artery and precapillary structures and evokes increase of intestinal oxygen uptake. This might be in part due to inhibition of sympathetic postganglionic fibers vasopressor activity. Central histamine H3 receptor stimulation activates vasoconstrictory sympathetic adrenergic system with possible involvement of other, presumably non-histaminergic receptors system. At basal conditions neither central nor peripheral histamine H3 receptors are involved in the control of mesenteric macro - and microcirculation and intestinal oxygen consumption.

3

Involvement of sensory afferent fibers and lipid peroxidation in the pathogenesis of stress-induced gastric mucosa damage

86%

Kwiecien S., Pawlik M. W., Sliwowski Z., Kwiecien N., Brzozowski T., Pawlik W. W., Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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2007

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tom 58

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nr 3

149-162

4

Gastroprotection by pentoxyfilline against stress-induced gastric damage. Role of lipid peroxidation, antioxidizing enzymes and proinflammatory cytokines

86%

Kwiecien S., Brzozowski T., Konturek P. C., Pawlik M. W., Pawlik W. W., Kwiecien N., Konturek S. J.

Journal of Physiology and Pharmacology

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2004

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tom 55

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nr 2

Impairment of blood perfusion in gastric mucosa results in the formation of erosions and ulcers. Nitric oxide (NO), produced via activity of NO-synthase (NOS), appears to be a one of major factors, involved in the regulation of the gastric blood flow (GBF). Inhibition of this enzyme by N-nitro-L-arginine (L-NNA) results in local decrease of NO production, reduces GBF and impairs gastric mucosal integrity, the effects that can be reversed by the pretreatment with L-arginine, the NOS substrate. However, little information is available regarding the contribution of reactive oxygen species (ROS)-induced lipid peroxidation and NO to the mechanism of gastric mucosal integrity. Therefore, the aim of our present study was to determine the action of pentoxyfilline (PTX), an inhibitor of tumor necrosis factor alpha (TNFalpha) with or without NOS inhibition by L-NNA administration in rats with water immersion and restraint stress (WRS)-induced gastric lesions . Experiments were carried out on 100 male Wistar rats. The gastric blood flow (GBF) was measured using laser Doppler flowmeter. The area of gastric lesions was determined by planimetry and the levels of proinflammatory cytokines (IL-1ß and TNFalpha) were measured by ELISA. Colorimetric assays were employed to determine gastric mucosal levels of lipid peroxidation products, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) and antioxidant enzymes including superoxide dismutase (SOD) activity, as well as tissue concentration of reduced glutathione (GSH). Administration of PTX significantly attenuated the gastric lesions, induced by 3.5 h of WRS and this was accompanied by the rise in the GBF and a significant decrease in plasma proinflammatory cytokines (IL-1ß and TNFalpha) levels, as well as the reduction of lipid peroxidation. Exposure of rats to WRS supressed the SOD and GSH activities and these effects were reversed by PTX. The protective and hyperemic effects of PTX, as well as an increase in mucosal SOD activity and GSH concentration were counteracted by pretreatment with L-NNA, but restored by the pretreatment with L-arginine, a NOS substrate. We conclude that PTX exerts beneficial, gastroprotective effect against WRS-induced gastric lesions due to enhancement in gastric microcirculation, possibly mediated by the enhanced NOS activity as well as local action of NO and by the attenuation of oxidative metabolism and generation proinflammatory cytokines.

5

The role of reactive oxygen species and capsaicin-sensitive sensory nerves in the pathomechanisms of gastric ulcers induced by stress

86%

Kwiecien S., Brzozowski T., Konturek P. C., Pawlik M. W., Pawlik W. W., Kwiecien N., Konturek S. J.

Journal of Physiology and Pharmacology

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2003

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tom 54

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nr 3

Gastric microcirculation plays an important role in the maintenance of the gastric mucosal barrier and mucosal integrity. Sensory nerves are involved in the regulation of mucosal blood circulation and mucosal defense. Therefore, the ablation of these nerves by neurotoxic doses of capsaicin provides the possibility of determination of their role in gastric mucosal integrity. Stress ulceration represents a serious gastric lesions. Results of our previous experiments have indicated that water immersion and restraint stress (WRS) led to increased oxidative metabolism. Ablation of sensory nerves by high doses of capsaicin retards healing of gastric ulcers, but the role of reactive oxygen species (ROS) in the healing process has been little studied. Therefore, the aim of our present investigations was to determine the participation of ROS in sensory nerve activity during WRS. Experiments were caried out on 90 male Wistar rats and the area of gastric lesions was measured by planimetry.Colorimetric assays were used to determine gastric mucosal levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), as well as superoxide dismutase (SOD) activity. We demonstrated that inactivation of sensory nerves resulted in magnification of gastric mucosal damage induced by the WRS. In this process, oxidative stress, as reflected by an increase of MDA and 4-HNE tissue concentrations (an index of lipid peroxidation), as well as decrease of SOD activity, could play an important role. Aspirin, applied in a low dose, exerts a protective activity, possibly due to its metabolites, which possess the anti-oxidant and ROS scavanging properties. Pentoxyfilline-induced gastroprotection and hyperemia depends upon attenuation of the oxidative stress. This protection and hyperemia were, at least in part, attenuated by ASA.

6

Histamine H3 receptors modulate reactive hyperemia in rat gut

86%

Pawlik W. W., Obuchowicz R., Pawlik M. W., Sendur R., Biernat J., Brzozowski T., Konturek S. J.

Journal of Physiology and Pharmacology

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2004

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tom 55

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nr 3

Reactive hyperemia (RH) is an abrupt blood flow increase following release from mechanical occlusion of an artery, with restoration of intra-arterial pressure. The mechanism of this postocclusion increase in blood flow in the gut is multifactorial. Relaxation of intestinal resistance vessels, observed during RH, may involve myogenic, metabolic, hormonal and neurogenic factors. Evidence exists that histamine is an important endogenous mediator of various functions of the gut, including blood flow. The vascular effects of histamine in the intestinal circulation are due its agonistic action on histamine H1, H2 and H3 receptors. In the present study the hypothesis was tested that peripheral histamine H3 receptors are involved in the mediation of RH in the intestinal circulation. In anesthetized rats, anterior mesenteric artery blood flow (MBF) was determined with ultrasonic Doppler flowmeter, and arterial pressure (AP) was determined with a transducer. The increase in the volume of blood accumulating during RH (RH-volume), the peak increase of arterial blood flow (RH-peak response) and the duration of the hyperemia (RH-duration) were used to quantify RH after occluding the anterior mesenteric artery for 30, 60 and 120 s. Hyperemia parameters were determined before and after administration of the selective histamine H3 receptor antagonist clobenpropit. Pretreatment with clobenpropit was without any effect on control MBF and AP but significantly reduced most of RH responses. These findings support the hypothesis that histamine H3 receptors do not play any role in the control of intestinal vasculature at basal conditions but these receptors participate in the intestinal hyperemic reaction in response to complete temporal intestinal ischemia.

7

Nitric oxide (NO)-releasing aspirin and (NO) donors in protection of gastric mucosa against stress

86%

Kwiecien S., Pawlik M. W., Brzozowski T., Konturek P. C., Sliwowski Z., Pawlik W. W., Konturek S. J.

Journal of Physiology and Pharmacology. Supplement

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2008

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tom 59

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nr 2

Acute gastric mucosal lesions represent an important clinical problem. The experimental model of acute gastritis such as water immersion restraint (WRS) stress is useful tool in examination of pathomechanism of acute gastric damage. Nitric oxide (NO) plays an important role in the maintenance of gastric barrier, however the role of reactive oxygen species (ROS) in the interaction between NO and gastric mucosa integrity has been little studied. The purpose of our present study was to explain the participation of ROS in healing of WRS-induced gastric lesions accelerated by NO. Experiments were carrying out on 120 male Wistar rats. To assess gastric blood flow (GBF) laser Doppler flowmeter was used. The number of gastric lesions was established by planimetry. The colorimetric assays were used to determine gastric tissue level of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), the products of lipid peroxidation by ROS, as well as superoxide dismutase (SOD) activity, the enzyme scavanger of ROS. We demonstrated that 3.5 h of WRS resulted in appearance of acute gastric mucosal lesions accompanied by a significant decrease of GBF. Biological effects of ROS were estimated by measuring tissue level of MDA and 4-HNE, as well as the SOD activity. It was demonstrated that 3.5 h of WRS led to significant increase of MDA and 4-HNE mucosal level, that was accompanied by a decrease of SOD activity. Pretreatment with NO-donors (SIN-1, SNAP, nitroglycerin, NO-ASA) resulted in reduction of gastric lesions number, increment of GBF, decrease of MDA and 4-HNE tissue level and increase of SOD activity. Suppression of ROS play an important role in NO-donors action in gastroprotection against gastric acute lesions induced by 3.5 h of WRS. NO-donors cause an attenuation of lipid peroxidation as documented by a decrease of MDA and 4-HNE levels and enhancement of antioxidative properties as evidenced by increase of SOD activity.

8

Interaction between selective cyclooxygenase inhibitors and capsaicin-sensitive afferent sensory nerves in pathogenesis of stress-induced gastric lesions. Role of oxidative stress

73%

Kwiecien S., Konturek P. C., Sliwowski Z., Mitis-Musiol M., Pawlik M. W., Brzozowski B., Jasnos K., Magierowski M., Konturek S. J., Brzozowski T.

Journal of Physiology and Pharmacology

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2012

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tom 63

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nr 2

9

Esophagoprotective activity of angiotensin-(1-7) in experimental model of acute reflux esophagitis. Evidence of the role of nitric oxide, sensory nerves, hypoxia-inducible factor-1alpha and proinflammatory cytokines

73%

Pawlik M. W., Kwiecien S., Pajdo R., Ptak-Belowska A., Brzozowski B., Krzysiek-Maczka G., Strzalka M., Konturek S. J., Brzozowski T.

Journal of Physiology and Pharmacology

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2014

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tom 65

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nr 6

10

Effects of peripherally and centrally applied ghrelin in the pathogenesis of ischemia-reperfusion induced injury of the small intestine

73%

Pawlik M. W., Obuchowicz R., Biernat J., Szczepanski W., Pajdo R., Kwiecien S., Brzozowski T., Konturek S. J., Pawlik W. W.

Journal of Physiology and Pharmacology

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2011

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tom 62

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nr 4

11

The renin-angiotensin system and its vasoactive metabolite angiotensin-(1-7) in the mechanism of the healing of preexisting gastric ulcers. The involvement of mas receptors, nitric oxide, prostaglandins and proinflammatory cytokines

59%

Pawlik M. W., Kwiecien S., Ptak-Bielowska A., Pajdo R., Olszanecki R., Suski M., Madej J., Targosz A., Konturek S. J., Korbut R., Brzozowski T.

Journal of Physiology and Pharmacology

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2016

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tom 67

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nr 1

Ograniczanie wyników

Transcriptional upregulation of gastrin in response to peroxisome proliferator-activated receptor gamma agonist triggers cell survival pathways

Involvement of central and peripheral histamine H3 receptors in the control of the vascular tone and oxygen uptake in the mesenteric circulation of the rat

Involvement of sensory afferent fibers and lipid peroxidation in the pathogenesis of stress-induced gastric mucosa damage

Gastroprotection by pentoxyfilline against stress-induced gastric damage. Role of lipid peroxidation, antioxidizing enzymes and proinflammatory cytokines

The role of reactive oxygen species and capsaicin-sensitive sensory nerves in the pathomechanisms of gastric ulcers induced by stress

Histamine H3 receptors modulate reactive hyperemia in rat gut

Nitric oxide (NO)-releasing aspirin and (NO) donors in protection of gastric mucosa against stress

Interaction between selective cyclooxygenase inhibitors and capsaicin-sensitive afferent sensory nerves in pathogenesis of stress-induced gastric lesions. Role of oxidative stress

Esophagoprotective activity of angiotensin-(1-7) in experimental model of acute reflux esophagitis. Evidence of the role of nitric oxide, sensory nerves, hypoxia-inducible factor-1alpha and proinflammatory cytokines

Effects of peripherally and centrally applied ghrelin in the pathogenesis of ischemia-reperfusion induced injury of the small intestine

The renin-angiotensin system and its vasoactive metabolite angiotensin-(1-7) in the mechanism of the healing of preexisting gastric ulcers. The involvement of mas receptors, nitric oxide, prostaglandins and proinflammatory cytokines