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Dive into the research topics where Sibel Ülker is active.

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Featured researches published by Sibel Ülker.


Cardiovascular Research | 2003

Impaired activities of antioxidant enzymes elicit endothelial dysfunction in spontaneous hypertensive rats despite enhanced vascular nitric oxide generation

Sibel Ülker; Dorothy McMaster; Pascal McKeown; Ulvi Bayraktutan

OBJECTIVE Enhanced oxidative stress is involved in mediating the endothelial dysfunction associated with hypertension. The aim of this study was to investigate the relative contributions of pro-oxidant and anti-oxidant enzymes to the pathogenesis of endothelial dysfunction in genetic hypertension. METHODS Dilator responses to endothelium-dependent and endothelium-independent agents such as acetylcholine (ACh) and sodium nitroprusside were measured in the thoracic aortas of 28-week-old spontaneously hypertensive rats (SHR) and their matched normotensive counterparts, Wistar Kyoto rats (WKY). The activity and expression (mRNA and protein levels) of endothelial nitric oxide synthase (eNOS), p22-phox, a membrane-bound component of NAD(P)H oxidase, and antioxidant enzymes, namely, superoxide dismutases (CuZn- and Mn-SOD), catalase and glutathione peroxidase (GPx), were also investigated in aortic rings. RESULTS Relaxant responses to ACh were attenuated in phenylephrine-precontracted SHR aortic rings, despite a 2-fold increase in eNOS expression and activity. Although the activity and/or expression of SODs, NAD(P)H oxidase (p22-phox) and GPx were elevated in SHR aorta, catalase activity and expression remained unchanged compared to WKY. Pretreatment of SHR aortic rings with the inhibitor of xanthine oxidase, allopurinol, and the inhibitor of cyclooxygenase, indomethacin, significantly potentiated ACh-induced relaxation. Pretreatment of SHR rings with catalase and Tiron, a superoxide anion (O(2)(-)) scavenger, increased the relaxant responses to the levels observed in WKY rings whereas pyrogallol, a O(2)(-)-generator, abolished relaxant responses to ACh. CONCLUSION These data demonstrate that dysregulation of several enzymes, resulting in oxidative stress, contributes to the pathogenesis of endothelial dysfunction in SHR and indicate that the antioxidant enzyme catalase is of particular importance in the reversal of this defect.


Journal of Diabetes and Its Complications | 2010

Apocynin restores endothelial dysfunction in streptozotocin diabetic rats through regulation of nitric oxide synthase and NADPH oxidase expressions

Murat Olukman; Cahide Elif Orhan; Fatma Gül Çelenk; Sibel Ülker

AIM Increased production of reactive oxygen species (ROS) in the diabetic vasculature results in the impairment of nitric oxide (NO)-mediated relaxations leading to impaired endothelium-dependent vasodilation. An important source of ROS is nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and the inhibition of this enzyme is an active area of interest. This study aimed to investigate the effects of apocynin, an NADPH oxidase inhibitor, on endothelial dysfunction and on the expression of NO synthase (NOS) and NADPH oxidase in thoracic aorta of diabetic rats. METHOD Streptozotocin (STZ)-diabetic rats received apocynin (16 mg/kg per day) for 4 weeks. Endothelium-dependent and -independent relaxations were determined in thoracic aortic rings. Western blotting and RT-PCR analysis were performed for NOSs and NADPH oxidase in the aortic tissue. RESULTS Acetylcholine-induced relaxations and l-NAME-induced contractions were decreased in diabetic aorta. The decrease in acetylcholine and l-NAME responses were prevented by apocynin treatment without a significant change in plasma glucose levels. Endothelial NOS (eNOS) protein and mRNA expression exhibited significant decrease in diabetes, while protein and/or mRNA expressions of inducible NOS (iNOS) as well as p22(phox) and gp91(phox) subunits of NADPH oxidase were increased, and these alterations were markedly prevented by apocynin treatment. CONCLUSION NADPH oxidase expression is increased in diabetic rat aorta. NADPH oxidase-mediated oxidative stress is accompanied by the decreased eNOS and increased iNOS expressions, contributing to endothelial dysfunction. Apocynin effectively prevents the increased NADPH oxidase expression in diabetic aorta and restores the alterations in NOS expression, blocking the vicious cycle leading to diabetes-associated endothelial dysfunction.


Life Sciences | 2003

Agmatine attenuates neuropathic pain in rats: Possible mediation of nitric oxide and noradrenergic activity in the brainstem and cerebellum

Aytül Önal; Yasemin Delen; Sibel Ülker; Necdet Soykan

Effect of agmatine (10-400 mg/kg) on neuropathic pain in a rat model produced by loose ligatures around the common sciatic nerve was studied. The involvement of possible alterations in nitric oxide (NO) levels [measured as its stable metabolites nitrate + nitrite] and in noradrenergic activity [measured as norepinephrine and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) levels] in this effect was also investigated biochemically in the brainstem and cerebellum. Agmatine increased the neuropathic pain threshold at 300 and 400 mg/kg. There was almost a twofold increase in nitrate + nitrite levels in the brainstem and cerebellum of the rats with neuropathic pain and agmatine decreased the high nitrate + nitrite levels only in the brainstem at 300 mg/kg and both in the brainstem and cerebellum at 400 mg/kg. Ligation of sciatic nerve resulted in almost twofold increase in norepinephrine and MHPG levels only in the brainstem of the rats. Agmatine decreased MHPG levels at 300 and 400 mg/kg, however it decreased norepinephrine levels only at the higher dose. These findings indicate that agmatine decreases neuropathic pain, an effect which may involve the reduction of NO levels and noradrenergic activity in the brain.


Pharmacology | 2001

Effect of dietary vitamin E supplementation on vascular reactivity of thoracic aorta in streptozotocin-diabetic rats.

Mehtap G. Çınar; Sibel Ülker; Gülinnaz Alper; Akgün Evinç

The present study evaluated the effect of dietary vitamin E supplementation (1,000 mg/kg chow) on the alterations in vascular reactivity of streptozotocin-diabetic aorta of Wistar rats. After 12 weeks of treatment, thoracic aortic rings of rats were mounted in organ baths and contractile responses to phenylephrine and 5-hydroxytryptamine and relaxant responses to acetylcholine, calcium ionophore and sodium nitroprusside were assessed. Plasma vitamin E concentration as measured by HPLC was markedly decreased in diabetic rats and increased with dietary vitamin E supplementation. Induction of diabetes significantly impaired endothelium-dependent relaxations to acetylcholine and calcium ionophore in aortic rings, but did not change endothelium-independent relaxation to sodium nitroprusside. Vitamin E significantly improved the impaired endothelium-dependent relaxations, further it decreased the enhanced contractile response to phenylephrine and 5-hydroxytryptamine in diabetic rings. The mechanical denudation of endothelium or the chemical inhibition of endothelium-dependent relaxation with Nω-nitro-L-arginine methyl ester (100 µmol/l) significantly increased phenylephrine contractility in control rings and the rings of diabetic rats treated with vitamin E; such a difference was not observed in diabetic rats fed with normal diet. Liver and lung malondialdehyde concentrations, as an index of lipid peroxidation, were increased in diabetic rats and significantly decreased with vitamin E supplementation. It is concluded that dietary supplementation of vitamin E improved endothelial dysfunction in insulin-dependent model of uncontrolled diabetes, probably decreasing membranal lipid peroxidation.


Experimental Diabetes Research | 2010

Fenofibrate Treatment Enhances Antioxidant Status and Attenuates Endothelial Dysfunction in Streptozotocin-Induced Diabetic Rats

Murat Olukman; Ebru Sezer; Sibel Ülker; Eser Yildirim Sözmen; Gülcihan Mehtap Çınar

Diabetic endothelial dysfunction is accompanied by increased oxidative stress and upregulated proinflammatory and inflammatory mediators in the vasculature. Activation of peroxisome proliferator-activated receptor-alpha (PPAR-α) results in antioxidant and anti-inflammatory effects. This study was designed to investigate the effect of fenofibrate, a PPAR-α activator, on the endothelial dysfunction, oxidative stress, and inflammation in streptozotocin diabetic rats. Diabetic rats received fenofibrate (150 mg kg−1 day−1) for 4 weeks. Fenofibrate treatment restored the impaired endothelium-dependent relaxation and increased basal nitric oxide availability in diabetic aorta, enhanced erythrocyte/liver superoxide dismutase and catalase levels, ameliorated the abnormal serum/aortic thiobarbituric acid reactive substances, and prevented the increased aortic myeloperoxidase without a significant change in serum total cholesterol and triglyceride levels. It did not affect the decreased total homocysteine level and the increased tumor necrosis factor-α level in the serum of diabetic rats. Fenofibrate-induced prevention of the endothelial function seems to be related to its potential antioxidant and antiinflammatory activity.


Pharmacology, Biochemistry and Behavior | 2007

Milnacipran attenuates hyperalgesia and potentiates antihyperalgesic effect of tramadol in rats with mononeuropathic pain

Aytül Önal; Ayşe Parlar; Sibel Ülker

Milnacipran is a non-tricyclic antidepressant drug which selectively inhibits serotonin and noradrenaline re-uptake and is recommended in the treatment of various chronic pain syndromes. Many studies have shown that compounds known to block monoamine uptake potentiate the antinociceptive effects of opioids. This study investigates the effect of milnacipran alone or in combination with an opiodergic drug, i.e. tramadol, on hyperalgesia in a rat model of neuropathic pain. The contribution of serotonergic, noradrenergic and opioidergic systems in the potential antihyperalgesic effect of milnacipran has also been examined. Chronic constriction injury was induced in rats by loose ligation of the sciatic nerve and neuropathic pain was evaluated 14 days after surgery. Intraperitoneal acute injection of milnacipran 60 mg/kg produced an antihyperalgesic effect which was prevented by pretreating systemically with alpha-methyl-p-tyrosine, an inhibitor of noradrenaline synthesis; parachlorophenylalanine, an inhibitor of serotonin synthesis; and naloxone, an antagonist of opioidergic receptors. Co-administration of milnacipran 40 mg/kg with tramadol (20 and 40 mg/kg) potentiated the antihyperalgesic effect of tramadol. Milnacipran has an antihyperalgesic effect mediated by serotonergic, noradrenergic and opioidergic systems and the combined use of tramadol with milnacipran potentiates the effect of tramadol in the management of neuropathic pain.


Diabetes, Obesity and Metabolism | 2004

Antioxidant vitamins C and E ameliorate hyperglycaemia‐induced oxidative stress in coronary endothelial cells

Sibel Ülker; Dorothy McMaster; Pascal McKeown; Ulvi Bayraktutan

Objective:  Vitamins C and E have protective features in many disease states associated with enhanced oxidative stress. The aim of this study was to investigate whether vitamin(s) C and/or E modulate hyperglycaemia‐induced oxidative stress by regulating enzymatic activities of prooxidant, i.e. NAD(P)H oxidase and/or antioxidant enzymes, namely endothelial nitric oxide synthase (eNOS), superoxide dismutase, catalase and glutathione peroxidase, using coronary microvascular endothelial cells (CMEC).


Diabetes-metabolism Research and Reviews | 2006

Effect of vitamin E and C supplementation combined with oral antidiabetic therapy on the endothelial dysfunction in the neonatally streptozotocin injected diabetic rat

Gülinnaz Alper; Murat Olukman; Seda İrer; Osman Caglayan; Erdal Duman; Candeger Yilmaz; Sibel Ülker

This study investigates the contribution of vitamin supplementation to the efficacy of oral antidiabetic therapy on the reversal of endothelial dysfunction in a model of type‐2 diabetes in rat.


Pharmacology | 2000

Role of Leukotrienes on Coronary Vasoconstriction in Isolated Hearts of Arthritic Rats: Effect of in vivo Treatment with CI-986, a Dual Inhibitor of Cyclooxygenase and Lipoxygenase

Şule Gök; Sibel Ülker; Afig Huseyinov; Funda Bölükbaşι Hatip; Mehtap G. Çınar; Akgün Evinç

In this study, coronary perfusion pressure and force of contraction were investigated in isolated hearts removed from arthritic rats by using the Langendorff method. A strong coronary vasoconstriction was determined in arthritic hearts which was associated with elevated levels of arachidonate 5-lipoxygenase (5-LOX) products, leukotriene B4 (LTB4) and LTC4 in coronary effluents. In vivo treatment with the dual inhibitor of cyclooxygenase (COX) and LOX, CI-986 (2 and 10 mg/kg/day) on days 14– 26 following adjuvant injection, prevented the coronary vasoconstriction and the increased production of LTB4 and LTC4. These results suggest that the coronary vasoconstriction in the isolated arthritic hearts is associated with an increased activity of the LOX system and CI-986 could have a preventive effect on constriction of coronary arteries.


Neuroscience Letters | 2010

Antihyperalgesic and antiallodynic effect of sirolimus in neuropathic pain and the role of cytokines in this effect.

Cahide Elif Orhan; Aytül Önal; Sibel Ülker

Recent studies have revealed that T lymphocytes play a role in neuropathic pain following nerve injury in rats through releasing several cytokines. Sirolimus is an immunosuppressive antibiotic inhibiting T cell activation. This study aimed to determine the effect of sirolimus on hyperalgesia and allodynia and on serum and spinal cord TNF-alpha, IL-1beta and IL-6 levels in rat neuropathic pain. Neuropathic pain was induced by loose ligation of the sciatic nerve and evaluated by tests measuring the mechanical hyperalgesia and allodynia. Sirolimus (0.75 and 1.5 mg/kg) was administered intraperitoneally once every 3 days for 2 weeks (7 doses totally). This dosing regimen revealed acceptable blood concentrations in neuropathic rats. Chronic constriction injury of the sciatic nerve resulted in hyperalgesia and allodynia. Serum levels of cytokines remained unchanged in neuropathic rats. However, TNF-alpha, but not IL-1beta or IL-6, protein level was increased in the spinal cord tissue as evaluated by Western blotting analysis. Treatment with sirolimus resulted in antihyperalgesic and antiallodynic effects and prevented the increased spinal cord TNF-alpha level. It seems that sirolimus could be a promising immunosuppressive agent in the treatment of neuropathic pain.

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Pascal McKeown

Queen's University Belfast

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