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    Antiepileptic effects of ghrelin on pentylenetetrazole-induced seizures in rats
    (Elsevier Science Inc, 2007) Obay, Basra Deniz; Tasdemir, Ezel; Tuemer, Cemil; Bilgin, Hakki Murat; Sermet, Abdurrahman
    It is well known that neuropeptide Y (NPY) and gamma-aminobutyric acid (GABA) exert antiepileptic effects in animal models. It has recently been shown that ghrelin neurons increase the activities of GABA and NPY in the brain. Therefore it can be said that ghrelin is an antiepileptic agent. In this study we aimed to investigate the antiepileptic effect of ghrelin in an acute experimental epilepsy model in pentylenetetrazole (PTZ) injected rats. Adult male Wistar albino rats were divided into a control group and four experimental groups with seven rats in each group. In order to generate epileptic seizures, PTZ (50 mg/kg) was injected intraperitone ally. The experimental groups received intraperitoneal injections of ghrelin at doses of 20,40, 60 and 80 mu g/kg 30 min before PTZ injection. After PTZ injection, the latencies were separated into three components: first myoclonic jerk, generalized clonic seizures and tonic generalized extension. The injection of 50 mg/kg PTZ-induced epileptic seizures in the control group. The onset-times of the three characteristic behavioral changes were significantly delayed and the duration of tonic generalized extension was diminished by dose-dependent ghrelin administration. Our results demonstrated that ghrelin suppresses the onset time of PTZ-induced seizures. In the light of our current knowledge, it seems that ghrelin may be considered as an antiepileptic drug. (c) 2007 Elsevier Inc. All rights reserved.
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    Comparison of the anti-diabetic effects of resveratrol, gliclazide and losartan in streptozotocin-induced experimental diabetes
    (Taylor & Francis Ltd, 2015) Yazgan, Umit Can; Tasdemir, Ezel; Bilgin, Hakki Murat; Obay, Basra Deniz; Sermet, Abdurrahman; Elbey, Bilal
    Aim: The aim of this study was to compare the effect of the resveratrol with gliclazide and losartan in streptozotocin induced diabetic rats. Materials and methods: Adult male Wistar albino rats were divided into five groups of seven rats each. Diabetes was induced with a single intraperitoneal (i.p.) injection of streptozotocin (55mg/kg). Rats with blood glucose levels above 250mg/dl after 48h of streptozotocin injection were included in the diabetic group. Gliclazide and resveratrol were administered for 3 weeks at 5mg/kg per day and losartan was administered for 3 weeks at 30mg/kg per day in an oral aqueous suspension. At the end of the third week all rats were euthanized and fasting blood glucose, HbA1c and the metabolic activity of the hepatic enzymes hexokinase and glucose-6 phosphate dehydrogenase were measured in tail blood and liver specimens. All parameters were quantified using an ELISA plate reader. Results: Resveratrol and gliclazide significantly reduced both blood glucose levels and HbA1c levels in diabetic rats (p<0.001). However, losartan did not exhibit the same effects (p<0.05). The enzymatic activity of the liver enzymes hexokinase, glucose-6 phosphate dehydrogenase, fructose 1,6-biphosphatase, pyruvate kinase and glucose-6 phosphatase were enhanced by resveratrol and gliclazide, while losartan treatment was not associated with significant changes in liver carbohydrate metabolism. Conclusion: Resveratrol was not effective in improving liver carbohydrate metabolism relative to gliclazide, a drug widely used to treat diabetes. Dose-response profile of resveratrol remains indeterminate and additional studies may be necessary to determine effective dosing in diabetes.
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    Dose dependent effects of ghrelin on pentylenetetrazole-induced oxidative stress in a rat seizure model
    (Elsevier Science Inc, 2008) Obay, Basra Deniz; Tasdemir, Ezel; Tuemer, Cemil; Bilgin, Hakki Murat; Atmaca, Mukadder
    It has been suggested that free oxygen radicals play a role in the genesis of epilepsy and in post-seizure neuronal death. The aim of this study was to investigate the dose dependent effect of ghrelin on pentylenetetrazole (PTZ)-induced oxidative stress in a rat seizure model. For this purpose, the ghrelin groups were treated with intraperitoneal injections of ghrelin at doses of 20, 40, 60 and 80 [mu g/kg before the PTZ injection. Superoxide dismutase (SOD) and catalase (CAT) activities, and reduced glutathione (GSH) and thiobarbituric acid-reactive substance (TBARS) levels were measured in erythrocytes, liver and brain tissue. TBARS, the indicator of lipid peroxidation, was significantly increased in erythrocytes, liver and brain tissue, while antioxidant enzyme activities and glutathione levels were significantly decreased in PTZ injected rats. Ghrelin pretreatment prevented lipid peroxidation and the reduction in antioxidant enzyme activities and GSH levels against PTZ-induced oxidative stress in a dose dependent manner. The present data indicates that PTZ at a convulsive dose induces an oxidative stress response by depleting the antioxidant defense systems and increasing lipid peroxidation in the erythrocytes, liver and brain of rats. Ghrelin pretreatment diminished oxidative stress and prevented the decrease in antioxidant enzyme activities, and thus may reduce neuronal death in the brain during seizures. However, further studies are needed in order to confirm our hypothesis. (c) 2007 Elsevier Inc. All rights reserved.
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    Effect of ghrelin administration on phagocytic activity in acute cold-restraint stress exposed rats
    (Elsevier, 2007) Tumer, Cemil; Bilgin, Hakki Murat; Obay, Basra Deniz; Diken, Huda; Tasdemir, Ezel; Sermet, Abdurrahman
    Ghrelin, an endogenous ligand for growth hormone secretagogue receptor, was identified in the rat stomach. This peptide acts through nitric oxide (NO) by expressing endothelial nitric oxide synthase (eNOS) and down regulating inducible nitric oxide synthase (NOS) at its gastroproprotective effect against restraint stress induced damage. Recently the glirelin receptor has also been detected in peripheral systems including immune tissue. We have investigated the possible effect of glirelin on phagocytic activity of peritoneal macrophages in acute coldrestraint stress (ACRS) exposed rats. The rats were divided into control, stress and ghrelin groups. In ghrelin groups, single dose and three days consecutive dose of ghrelin (20 mu g/kg. i.p.) were applied to rats that were exposed to ACRS for 4 h. I rut of saline was injected i.p. after ACRS for 3 consecutive days to the rats of the stress groups. Ghrelin administration reduced the increased phagocytic activity induced by ACRS. We conclude that ghrelin exerts an important role at macrophage phagocytic activity in ACRS exposed rats. (c) 2006 Elsevier B.V. All rights reserved.
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    Effect of ghrelin on gastric myoelectric activity and gastric emptying in rats
    (Elsevier, 2008) Tumer, Cemil; Oflazoglu, Hueda Diken; Obay, Basra Deniz; Kelle, Mustafa; Tasdemir, Ezel
    Ghrelin is a recently discovered peptide in the endocrine cells of the stomach, which may stimulate gastric motility via the vagal nerve pathway. However, the mechanism of ghrelin-induced changes in gastrointestinal motility has not been clearly defined. The purpose of this study was to investigate the pharmacological effects of ghrelin on gastric myoelectrical activity and gastric emptying in rats, and to investigate whether cholinergic activity is involved in the effects of ghrelin. The study was performed on Sprague-Dawley rats implanted with serosal electrodes for electrogastrographic recording. Gastric slow waves were recorded from fasting rats at baseline and after injection of saline, ghrelin, atropine, or atropin+ghrelin. Gastric emptying of non-caloric liquid was measured by the spectrophotometric method in conscious rats. Intravenous administration of rat ghrelin (20 mu g/kg) increased not only dominant frequency, dominant power and regularity of the gastric slow wave but also the gastric emptying rate when compared with the control rats (P < 0.01, P < 0.05, P < 0.05, P < 0.001 respectively). These stimulatory actions of ghrelin on both gastric myoelectrical activity and gastric emptying were not fully eliminated by pretreatment with atropine sulphate. These results taken together suggest that ghrelin may play a physiological role in the enteric neurotransmission controlling gastric contractions in rats. (c) 2007 Elsevier B.V. All rights reserved.
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    Influence of coumarin and some coumarin derivatives on serum lipid profiles in carbontetrachloride-exposed rats
    (Sage Publications Ltd, 2017) Tasdemir, Ezel; Atmaca, Mukadder; Yildirim, Yasar; Bilgin, Hakki Murat; Demirtas, Berjan; Obay, Basra Deniz; Kelle, Mustafa
    In the present study, coumarin and some coumarin derivatives (esculetin, scoparone, and 4-methylumbelliferone) were investigated for their lipid-lowering effect in rats. Male Sprague-Dawley rats (150-200 g) were divided into six groups and each group comprised of five rats. Hepatic injury-dependent hyperlipidemia was induced by carbon tetrachloride (CCl4, 1.25 ml/kg). Coumarin and coumarin derivatives esculetin (35 mg/kg), scoparone (35 mg/kg), 4-methylumbelliferone (35 mg/kg), or coumarin (30 mg/kg) were administered to experimental groups at 12-h intervals. Animals received the derivatives esculetin, scoparone or 4-methylumbelliferone prior to the administration of a single toxic dose of CCl4. Serum total cholesterol (TC), triglyceride (TG), very low-density lipoprotein cholesterol (VLDL-C), and low-density lipoprotein cholesterol (LDL-C) levels significantly increased in CCl4-treated group (p < 0.05, p < 0.01, p < 0.01, and p < 0.05, respectively), while levels of serum high-density lipoprotein cholesterol (HDL-C) decreased (p < 0.01). 4-Methylumbelliferone had no recovery effects on serum TC levels, however, significantly prevented CCl4-induced hyperlipidemia by reducing TG and VLDL-C levels (p < 0.05 and p < 0.05, respectively). In addition, coumarin had no recovery effect on any of the serum lipid parameters against CCl4-induced hyperlipidemia. Among the coumarin derivatives only esculetin and scoparone significantly prevented serum HDL-C in CCl4-induced dyslipidemia. The results from this study indicate that the chemical structure of coumarins plays an important role on the regulation of serum lipid profiles.
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    Investigation of the Serum Visfatin, Fetuin A and Eotaxin Levels in Patients with Type 2 Diabetes Mellitus
    (Wiley, 2017) Kaya, Hacer; Sermet, Abdurrahman; Tasdemir, Ezel; Pekkolay, Zafer
    [Abstract Not Available]
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    Protective effects of coumarin and coumarin derivatives against carbon tetrachloride-induced acute hepatotoxicity in rats
    (Elsevier Gmbh, Urban & Fischer Verlag, 2011) Bilgin, Hakki Murat; Atmaca, Mukadder; Obay, Basra Deniz; Ozekinci, Selver; Tasdemir, Ezel; Ketani, Aydin
    The comparison of the antioxidant activity of some coumarins with their molecular structure is well determined. However, the protective function of coumarins with various chemical structures against liver toxicity has not yet been well established. Therefore, the aim of this study was to evaluate the possible cytoprotective properties of coumarin and some coumarin derivatives against CCl(4) (carbon tetrachloride)-induced hepatotoxicity. Coumarin (1,2-benzopyrone) and coumarin derivatives esculetin (6,7-dihydroxycoumarin), scoparone (6,7-dimethoxycoumarin) and 4-methylumbelliferone (7-hyroxy-4-methyl) were examined for their protective effect against CCl(4)-induced hepatotoxicity in Male Sprague-Dawley rats. A single toxic dose of CCl(4) (1.25 ml kg(-1), orally) produced liver damage in rats, seen histologically as centrilobular necrosis. Administration of CCl(4) increased serum enzyme levels of aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP). Pretreatment of rats with esculetin (31.15 mg kg(-1), orally) and scoparone (35 mg kg(-1), orally) significantly prevented CCl(4)-induced increase in serum enzymes, whereas 4-methylumbelliferone (35 mg kg(-1)) and coumarin (30 mg kg(-1)) had no effect against CCl(4)-induced rise in serum enzymes. Morphological findings were consistent with the plasma transaminase observations. Among the coumarin analogs, esculetin, which possesses orthodihydroxy coumarins, showed the strongest protective effect against CCl(4)-induced liver damage, followed by scoparone, 4-methylumbelliferone and coumarin, respectively. The results of this study indicate that the chemical structures of coumarins play an important role in the prevention of liver toxicity. (C) 2010 Elsevier GmbH. All rights reserved.
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    The role of monoamine oxidases in diabetic nephropathy rat model Diabetic nephropathy model
    (Bayrakol Medical Publisher, 2019) Tasdemir, Ezel; Sermet, Abdurrahman
    Aim: Diabetic nephropathy (DN) is a serious complication that can lead to renal failure in many diabetic patients. Although there are multiple mechanisms related to the pathogenesis of the disease, reactive oxygen species (ROS) play an important role in its etiology. It has been suggested that monoamine oxidases (MAOs) as an intracellularly important ROS source may cause nephropathy by contributing to redox state imbalance in the kidney of diabetics. We investigated the role of monoaminoxidase-A (MAO-A) and monoaminoxidase-B (MAO-B) in the pathogenesis of diabetic nephropathy (DN) induced by streptozotocin (STZ) in rats. We also tried to demonstrate the importance of MAO-A or MAO-B inhibition to prevent the development and progression of DN. Material and Method: Twenty-eight male Wistar albino rats were divided into four groups as normal control and three diabetic groups. A single dose of STZ was given to the peritoneal cavity of rats to induce diabetes. One of the diabetic groups was treated with MAO-A inhibitor(moclobemide, 5 mg/kg/day), another group MAO-B inhibitor, (rasagiline, 10 mg/kg/day), while those included in the DN group were not treated. After the eight-week treatment period, urine samples were collected with a metabolic cage to measure N -acethyl-b-glucosaminidase (NAG), g-glutamyltranspeptidase (GGT), creatinine, glucosuria and proteinuria, and then the animals were anesthetized and sacrificed by cardiac puncture and the kidneys were taken. Blood glucose, BUN, serum creatinine, renal MAO-A, MAO-B, superoxide dismutase (SOD) and catalase (CAT) activity and lipid peroxidation (MDA) were determined by spectrophotometric or ELISA method. Results: The untreated diabetic rats showed nephropathy symptoms such as high serum creatinine, proteinuria, glucosuria and high urinary NAG and GGT. However, renal MAO-A, MAO-B, SOD and CAT activity and MDA levels increased in DN rats. Although moclobemide or rasagiline treatment significantly reduced nephropathic findings and high renal MAO-A and MAO-B activity in diabetic rats, MAO-A inhibition showed more effect than MAO-B. Discussion: The results indicate that the renal MAO-A and MAO-B activity playsan important pathophysiological role, which is responsible for the development and progression of DN, and that MAO-A inhibition is more effective than MAO-B to prevent the formation of DN in diabetic rats.
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    TIME-DEPENDENT CHANGES IN PLASMA GHRELIN AND ANGIOTENSIN II LEVELS IN THE DIABETIC NEPHROPATHY MODEL
    (Parlar Scientific Publications (P S P), 2021) Gul, Cihan; Kelle, Mustafa; Baylan, Mukadder; Yokus, Beran; Tasdemir, Ezel
    Ghrelin is an appetite-enhancing anabolic hormone secreted from the stomach. Angiotensin II maintains sodium and potassium levels in body fluids and plays a very important role in the regulation of arterial blood pressure. Although their relationship with Type 2 diabetes and complications have been reported, their role in diabetic nephropathy is not fully understood. We investigated time dependent possible changes in plasma ghrelin and angiotensin II levels during the development and progression of diabetic nephropathy in experimental diabetic rat model. Adult 63 male Wistar Albino rats were randomly divided into 9 groups as 4 control (C1-C4), 4 diabetic (D1-D4) and one treatment (T) group. Group D1, sacrificed by cardiac puncture one week after diabetes, group D2 three weeks later, group D3 six weeks later, and groups D4 and T eight weeks later. Antidiabetic treatment was not administered to the D1-D4 group diabetic rats. Group T diabetic rats were treated with antidiabetic metformin (100 mg / kg / day) for 8 weeks. A single dose of 35 mg / kg intraperitoneal streptozotocin was administered to the rats to induce diabetes. Significant differences were found between the D4 and C4 groups in body weight, plasma glucose, ghrelin and angiotensin II, serum and urine creatinine levels. While there was a linear (positive) relationship between plasma ghrelin levels of all rats and urinary creatinine and creatinine clearance and body weight, negative correlations were found between plasma ghrelin and angiotensin II levels and fasting blood glucose levels of all rats. During the progression of diabetes and the development of diabetes-related nephropathy, plasma angiotensin and serum creatinine levels increased, while plasma ghrelin levels decreased over time. Therefore, it was concluded that changes in plasma ghrelin and angiotensin II levels in diabetic rats may be associated with the pathogenesis of diabetic nephropathy.