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Öğe 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, AbdurrahmanIt 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.Öğe 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, BilalAim: 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.Öğe Comparison of the effect of local microvibration and pulsed electromagnetic field application on bone fracture(Wiley-Blackwell, 2015) Bilgin, Hakki Murat; Celik, Ferhat; Akpolat, Veysi; Yildiz, Ismail; Ekinci, Aysun; Gem, Mehmet[Abstract Not Available]Öğe 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, MukadderIt 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.Öğe Effect of 900-, 1800-, and 2100-MHz radiofrequency radiation on DNA and oxidative stress in brain(Taylor & Francis Inc, 2019) Alkis, Mehmet Esref; Bilgin, Hakki Murat; Akpolat, Veysi; Dasdag, Suleyman; Yegin, Korkut; Yavas, Mehmet Cihan; Akdag, Mehmet ZulkufUbiquitous and ever increasing use of mobile phones led to the growing concern about the effects of radiofrequency radiation (RFR) emitted by cell phones on biological systems. The aim of this study is to explore whether long-term RFR exposure at different frequencies affects DNA damage and oxidant-antioxidant parameters in the blood and brain tissue of rats. 28 male Sprague Dawley rats were randomly divided into four equal groups (n = 7). They were identified as Group 1: sham-control, Group 2: 900 MHz, Group 3: 1800 MHz, and Group 4: 2100 MHz. Experimental groups of rats were exposed to RFR 2 h/day for 6 months. The sham-control group of rats was subjected to the same experimental condition but generator was turned off. Specific absorption rates (SARs) at brain with 1 g average were calculated as 0.0845 W/kg, 0.04563 W/kg, and 0.03957, at 900 MHz, 1800 MHz, and 2100 MHz, respectively. Additionally, malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), total antioxidant status (TAS), and total oxidant status (TOS) analyses were conducted in the brain tissue samples. Results of the study showed that DNA damage and oxidative stress indicators were found higher in the RFR exposure groups than in the sham-control group. In conclusion, 900-, 1800-, and 2100-MHz RFR emitted from mobile phones may cause oxidative damage, induce increase in lipid peroxidation, and increase oxidative DNA damage formation in the frontal lobe of the rat brain tissues. Furthermore, 2100-MHz RFR may cause formation of DNA single-strand breaks.Öğe 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, AbdurrahmanGhrelin, 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.Öğe Effect of nitric oxide on phagocytic activity of lipopolysaccharide-induced macrophages(Wiley, 2007) Tumer, Cemil; Bilgin, Hakki Murat; Obay, Basra Deniz; Diken, Huda; Atmaca, Mukadder; Kelle, MustafaAmong the antimicrobial mechanisms associated with macrophages, NO produced by iNOS plays a major role in intracellular killing, but the relationship between NO and phagocytic activity after injection of inflammatory agents into the peritoneal cavity is not clear. The aim of the present study was to investigate the effect of nitric oxide (NO) on macrophage function after treatment with intraperitoneal lipopolysaccharide (LPS) and the role of exogenous L-arginine administration in this event. Six experimental groups and one control group, each consisting of seven Wistar rats were used: Group I: Control; Group II: LPS; Group III: LPS + L-arginine; Group IV: LPS + L-arginine + Aminoguanidine; Group V: LPS + Aminoguanidine; Group VI: L-arginine; Group VII: Aminoguanidine. Macrophage phagocytic activity and total plasma nitrite levels were increased in the LPS group. In the LPS + L-arginine group, both the phagocytic activity and total plasma nitrite levels showed large increases. Administration of aminoguanidine (AG), a specific iNOS inhibitor, abolished macrophage phagocytic activity and total plasma nitrite levels in the LPS and LPS + L-arginine groups. As a result, we showed that NO produced by macrophages has a role not only in intracellular killing, but also in phagocytic activity. (c) 2006 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.Öğe Effects of increasing ratio of progesterone in estrogen/progesterone combination on total oxidant/antioxidant status in rat uterus and plasma(Springer Heidelberg, 2010) Hekimoglu, Askin; Bilgin, Hakki Murat; Kurcer, Zehra; Ocak, Ali RizaThe relationship between increasing ratio of progesterone in estrogen/progesterone combination and oxidative stress (OS) was investigated. Thirty non-pregnant Wistar Albino female rats were divided into five groups and bilaterally ovariectomized (Ovx) except sham group. Sham + 0.3 cc seaseme oil, Ovx + 0.3 cc seaseme oil, Ovx + estradiol propionate (E2) (1 mu g/kg), Ovx + E2 + medroxyprogesterone acetate (MPA) 1 mg/kg, Ovx + E2 + MPA 20 mg/kg. Hormones were applied for three consecutive days after 28 days of ovariectomy. Their uteri and blood samples were collected and nitric oxide (NO), malondialdehyde (MDA), total oxidative status (TOS) and total antioxidant capacity (TAC) levels were determined. E2 + MPA1 treatment decreased NO, MDA and TOS levels and increased TAC levels in uterus. Plasma NO levels elevated in all groups and MDA production increased due to E2 treatment when compared to ovariectomy. E2 + MPA20 treatment increased TOS levels, while TAC levels decreased when compared to ovariectomy in plasma. Using E2 plus low dose progesterone may prevent pathologies resourced of OS.Öğe The hepatoprotective effect of coumarin and coumarin derivates on carbon tetrachloride-induced hepatic injury by antioxidative activities in rats(Springer, 2011) Atmaca, Mukadder; Bilgin, Hakki Murat; Obay, Basra Deniz; Diken, Huda; Kelle, Mustafa; Kale, EbruCoumarins are a vast group of natural compounds and some of them possess antioxidant activities. The comparison of the antioxidant activity of some coumarins with various chemical molecular structure has not been investigated in previous studies. Therefore, this study was aimed to investigate the hepatoprotective effect against carbon tetrachloride (CCl4) -induced hepatic injury by coumarin (1,2-benzopyrone) and coumarin derivatives, esculetin (6,7-dihydroxycoumarin), scoparone (6,7-dimethoxycoumarin), and 4-methylumbelliferone (7-hyroxy-4-methyl) in male Sprague-Dawley rats. Product of lipid peroxidation, malondialdehyde (MDA), activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) were evaluated for oxidative stress in hepatic injury. Gamma glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH) were detected in plasma as a biomarker of hepatic injury. Significantly elevated levels of MDA and lowered levels of SOD and CAT activities were observed in liver of rats exposed to CCl4, when compared to control values. Similarly, administration of CCl4 increased LDH and GGT levels in serum. Pre-treatment of rats with esculetin (35 mg kg(-1), orally) and scoparone (35 mg kg(-1), orally) significantly prevented CCl4-induced decrease in MDA levels and increase in SOD and CAT, whereas 4-methylumbelliferone (35 mg kg(-1)) and coumarin (30 mg kg(-1)) had no effect against CCl4-induced rise in serum enzymes. Esculetin and scoparone also showed protective properties as was evidenced in reduced LDH and GGT levels in serum. The results of this study indicate that the chemical structures of coumarins play an important role in the prevention of oxidative stress.Öğe 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, MustafaIn 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.Öğe Investigation of the effects of pulsed electromagnetic fields and calcium-channel blockers on osteogenesis(Wiley-Blackwell, 2016) Bilgin, Hakki Murat; Agacayak, Serkan; Akpolat, Veysi; Yildiz, Ismail[Abstract Not Available]Öğe 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, AydinThe 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.