Person: YÜKSEL, MERAL
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YÜKSEL
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Publication Metadata only Oxygen radicals and nitric oxide in rat mesenteric ischaemia-reperfusion: Modulation by L-arginine and N-G-nitro-L-arginine methyl ester(WILEY, 1998) YALÇIN, AHMET SUHA; Haklar, G; Ulukaya-Durakbasa, C; Yuksel, M; Dagli, T; Yalcin, AS1. The aims of the present study were to detect changes in superoxide anion (O-2(.-)), nitric oxide (NO) and other reactive oxygen species (ROS) directly by measurement of chemiluminescence (CL) and to investigate the role of L-arginine, a nitric oxide synthase (NOS) substrate, and N-G-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, together with their molecular enantiomers D-arginine and D-NAME, in a rat mesenteric ischaemia-reperfusion (I/R) model. 2, Seventy-nine female Wistar albino rats were divided into eight groups, The first three groups underwent sham operation; group 1 was the control group, group 2 received L-arginine and group 3 received L-NAME. Ischaemia was produced in the remaining five groups by ligation of the superior mesenteric artery for 30 min followed by 60 min reperfusion, Group 4 rats were control I/R rats and groups 5-8 received either L-arginine, L-NAME, D-arginine or D-NAME, respectively. 3, Both luminol and lucigenin CL was significantly increased in I/R groups compared with sham-operated groups. L-Arginine significantly reduced CL measurements. D-Arginine was also protective, but not as much as L-arginine. Both L- and D-arginine had in vitro O-2(.-)-scavenging potential, as tested by the xanthine-xanthine oxidase system. N-G-Nitro-L-arginine methyl ester decreased lipid peroxidation values in addition to reducing CL measurements. Nitric oxide concentrations were significantly increased in VR groups in comparison with sham-operated groups. Peroxynitrite formation was increased by I/R. Treatment with L-NAME was beneficial by reducing NO concentrations in the reperfused ileum, 4, In our I/R model, O-2(.-), NO and other ROS were increased. Although NOS inhibitors were effective in reducing oxidative damage, increasing NO concentrations with L-arginine was also beneficial, presumably due to the ability of L-arginine to inhibit phagocyte adherence and its radical scavenging potential. In fact, NO may have different effects in terms of tissue injury or protection depending on the concentration of oxygen and the haemodynamic state of the tissue.Publication Metadata only The multidisciplinary approach to biochemistry laboratory education(TURKISH BIOCHEM SOC, 2013) HAKLAR, GONCAGÜL; Erkoc, Figen; Sepici-Dincel, Aylin; Kayrin, Levet; Ozkan, Yesim; Eksioglu, Subhan; Yuksel, Meral; Haklar, Goncagul; Yavuz, Ozlem; Celik, Haydar; Konuk, Muhsin; Kurban, Sevil; Uysal, Hamdi; Kisa, Ucler; Bodur, Ebru; Selvi, Meryem; Akca, Gulcin; Simsek, BolkanEuropean Union's Life Long Learning Programmes and the Bologna Process describe new classifications. Related with these new classifications, our higher education system is being restructured under the name of National Qualification Frameworks. Between the National and European programmes comparability and the transparency is expected to promote life-long learning. The workshop named as Biochemistry Laboratory Training Workshop on Multi-Disciplinary Approach was held on 3-4 May 2012 in Ankara with the scope of biochemistry laboratory culture, education, laboratory work and experimental methodology consisted of gain and the development of scientific thinking skills. As a result of the workshop, it was mentioned that, biochemistry theoretical course and biochemistry laboratory are being taught in different faculties, colleges and vocational schools. Biochemistry's interdisciplinary character, its' being closely related to physiology, being based on chemistry/physics principles and conceptions and extending increasingly to molecular biology, molecular genetics and nanoscience have brought new approaches in Biochemistry and Biochemistry Laboratory Education. The need for developing new applications using alternative materials leads to modern experimentation to be employed in teaching biochemistry laboratory at different educational establishments. Taking into account the previous studies, the core laboratory training, achievements and targets identified. The timetable of the teaching-learning and the evaluation process were discussed. Besides the core laboratory programme, the awareness of scientific research projects was discussed. It was also noted the coordination between the different programmes and the basic mandatory structure of the laboratories during the time of adaptation to the European. In addition, difficulties in provision of equipment and supplies, the responsibility of governments, readiness and competencies of students, teaching staff qualifications were discussed for the effective laboratory training. Young scientists and graduate students had actively participated in the workshop. Finally positive steps have been taken to develop the ability to work with the cultures of scientific thinking.Publication Metadata only The effect of azithromycin on reactive oxygen species in rosacea(WILEY, 2007) HAKLAR, GONCAGÜL; Bakar, O.; Demircay, Z.; Yuksel, M.; Haklar, G.; Sanisoglu, Y.Background: Recent evidence suggests that inflammation in rosacea is associated with generation of reactive oxygen species (ROS) that are released by inflammatory cells. The efficacy of current therapeutic agents for rosacea such as tetracyclines and metronidazole has also been attributed to their antioxidant properties. Recently, a macrolide antibiotic, azithromycin, has been found to be an effective alternative in the treatment of rosacea. Aim: We planned a study to evaluate the antioxidant effects of azithromycin on ROS in rosacea. We compared basal ROS concentrations measured in the facial skin of patients with rosacea with the post-treatment levels and with those of healthy controls. Methods: Facial skin biopsies of 17 papulopustular patients with rosacea and 25 healthy controls were taken. Rosacea patients were assigned to receive oral azithromycin 500 mg on three consecutive days each week for 4 weeks. The total number of inflammatory lesions (the sum of papules and pustules) on the face of each patient with rosacea was counted at each visit. The luminol- and lucigenin-enhanced chemiluminescence (CL) levels of patients with rosacea were measured before and after 4 weeks of treatment and compared with those of healthy controls. Results: Rosacea patients had higher ROS levels than healthy controls (P < 0.001). A statistically significant decrease of both luminol- and lucigenin-enhanced CL levels were observed in patients with rosacea after treatment with azithromycin (t = 4.602, P < 0.001; vs. t = 4.634, P < 0.001, respectively). Conclusion: Rosacea patients have higher ROS levels than healthy controls. The results of our study support the antioxidant properties of azithromycin in rosacea.Publication Metadata only Nitric oxide and endothelin relationship in intestinal ischemia/reperfusion injury (II)(CHURCHILL LIVINGSTONE, 2001) DAĞLI, EMRULLAH TOLGA; Ozel, SK; Yuksel, M; Haklar, G; Durakbasa, CU; Dagli, TE; Aktan, AOEndothelins (ETs) are potent vasoconstrictors derived from vascular endothelium. They have primary roles in many pathophysiologic states including ischemia/reperfusion (I/R) injury. The relationships between nitric oxide (NO) and ETs are still under investigation. In this study on rats we want to focus on the interaction of NO and ET especially in I/R injury. For this purpose ET-1 and PD-156252, a nonselective ET receptor blocker, were given in a mesenteric I/R model and reactive oxygen species were detected directly using chemiluminescence of the ileal tissue. ET administrations to sham and I/R groups caused significant increases in NO concentrations whereas, in terms of peroxynitrite, which is a highly reactive group of free radicals, its increasing effects were seen only in I/R groups. This suggests that in I/R where superoxide levels increase together with NO, the conversion to peroxynitrite is likely and this effect is augmented with ET administration. On the other hand PD administration decreases superoxide and thereby peroxynitrite levels and this study shows that the effect of PD-156252 is established through this mode of action. These data suggest therapeutic approaches that may be beneficial in the treatment of I/R injury. (C) 2001 Harcourt Publishers Ltd.Publication Metadata only Iron preloading aggravates nutritional steatohepatitis in rats by increasing apoptotic cell death(ELSEVIER, 2007) EREN, FATİH; Imeryuz, Nese; Tahan, Veysel; Sonsuz, Abdullah; Eren, Fatih; Uraz, Suleyman; Yuksel, Meral; Akpulat, Sertac; Ozcelik, Dervis; Haklar, Goncagul; Celike, Cigdem; Avsar, Erol; Tozun, NurdanBackground/Aims: High serum ferritin and liver iron concentrations were found in some patients with NASH, suggesting a role for iron as a co-factor that aggravates liver injury. The aim of this study is to investigate the effects of parenteral iron in a rat model of NASH induced by a methionine choline deficient diet (MCDD). Methods:Wistar rats were divided into 1 - Control, 2 - Iron (Fe), 3 - MCDD, 4 - MCDD&Fe groups. Iron dextran 100 mg/kg was administered intra-muscularly in groups 2 and 4. All rats were fed MCDD, Groups I and 2 were supplied with choline and methionine. Blood and tissue samples were obtained after 4 weeks. Results: The iron injection alone did not affect the liver whereas MCDD led to steatohepatitis. Iron worsened steatosis without any obvious effect on accompanying inflammation. It aggravated tissue injury by increasing apoptosis. Liver fibrosis was observed only in 3 out of 10 rats in the MCDD&Fe group. Conclusions: Observation of liver fibrosis only in the MCDD&Fe group suggests that iron induced increase in apoptosis contributes to the development of fibrosis at an earlier time than expected. (c) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.Publication Metadata only Determination of reactive oxygen species in myringotomized tympanic membranes: Effect of vitamin E treatment(WILEY, 2004) HAKLAR, GONCAGÜL; Polat, S; Ozturk, O; Uneri, C; Yuksel, M; Haklar, G; Bozkurt, S; Kullu, SObjectives/Hypothesis: Recent studies have established a strong relationship between the development of myringosclerosis and reactive oxygen species (ROS). The aims of the present study were to directly detect ROS in the tympanic membrane and middle ear mucosa of rats by measuring luminol amplified chemiluminescence, to evaluate the changes in the levels of ROS after treatment with vitamin E, and to examine the possible changes in the tympanic membranes otomicroscopically and histologically. Study Design: Prospective controlled animal study. Methods: Forty healthy Sprague-Dawley rats were divided into five groups of eight animals each. Animals in all groups except group 1 were bilaterally myringotomized. Group 2 received no treatment, group 3 was treated with topical olive oil, group 4 received topical vitamin E, and group 5 received intramuscular vitamin E. After 24 hours of myringotomy, tympanic membranes were examined otomicroscopically; thereafter, tympanic membranes and middle ear mucosa were peeled off. The right ears of the animals were used for biochemical assay, and the left ears were used for histological study. Results: Reactive oxygen species levels were significantly decreased in group 4 with topical application of vitamin E compared with untreated and myringotomized animals in group 2. Reactive oxygen species levels were also decreased in group 5, although the decrease was not statistically significant when compared with groups 2 and 3. Histological studies confirmed sclerotic changes in the untreated myringotomized animals. The tympanic membranes of animals in groups 2 and 3 showed a white, chalk-like pattern of sclerotic changes, whereas animals in groups 4 and 5, with the exception of two animals in group 5, lacked these changes. Conclusion: Although the relationship between the development of myringosclerosis and ROS had been well documented previously, the present study is the first that has directly measured the levels of ROS in the tympanic membrane and middle ear mucosa. These results are relevant because they correlate with histological findings. It has also been demonstrated that topically applied vitamin E is effective in decreasing the ROS levels.Publication Metadata only Nitric oxide and endothelin relationship in intestinal ischemia/reperfusion injury(1998) DAĞLI, EMRULLAH TOLGA; Durakbasa, C. U.; Dagli, T. E.; Mouni, H.; Haklar, G.; Bilsel, A. S.; Yuksel, M.; Aktan, A. O.Gastrointestinal mucosal blood flow is dependent on a balanced release of vasoactive substances from endothelium. Nitric oxide (NO) may increase the flow by vasodilatation and/or antiaggregation whereas endothelin (ET) may decrease it by vasoconstriction and aggregation. NO and ET may have counterbalancing effects on each other in tissue damage. In order to test this hypothesis, in this study on rats, L-arginine to increase NO levels and N(G)-nitro-L-arginine methyl esther (L-NAME) to decrease NO levels have been used in an intestinal ischemia/ reperfusion (I/R) injury model and portal vein ET response was evaluated. Lipid peroxidation product measurements and chemiluminescence (CL) studies were also carried out in ileal tissue samples. Intestinal I/R injury caused an increase in portal venous ET levels with levels of 9.4+/-0.5 fmol/ml in sham operation and 14.8+/-1.6 fmol/ml in I/R group. ET level of L-NAME-sh group was lower than that of sham-operated group and also ET level of L-NAME-I/R group was lower than that of I/R group. This yielded the conclusion that inhibition of NO synthesis decreases portal venous ET levels in this model. Increased NO production by L-arginine caused increased ET levels in sham operated groups but this effect was not observed in I/R injury state. This study also showed that inhibition of NO synthesis has a protective role by reducing the reperfusion damage in this model. It is likely that NO and ET have a feedback effect on each other both under physiologic conditions and I/R injury.Publication Metadata only Rosiglitazone attenuates liver inflammation in a rat model of nonalcoholic steatohepatitis(SPRINGER, 2007) ÇELİKEL, ÇİĞDEM; Tahan, Veysel; Eren, Fatih; Avsar, Erol; Yavuz, Dilek; Yuksel, Meral; Emekli, Ebru; Imeryuz, Nese; Celikel, Cigdem; Uzun, Hafize; Haklar, Goncagul; Tozun, NurdanRosiglitazone is an insulin-sensitizing agent. We aimed to assess the effects of rosiglitazone on a methionine- and choline-deficient diet (MCDD) model of nonalcoholic steatohepatitis (NASH) in rats. Wistar rats were fed either MCDD or a control diet in the 4-week induction study; they were given saline or 4 mg/kg/day rosiglitazone. After the induction study period, the rats were divided into four groups and fed MCDD or given a control diet for an additional 8 weeks and received saline or rosiglitazone. Serum and tissue samples were obtained. Rosiglitazone improved inflammation in NASH and improved ALT, alkaline phosphatase, and interleukin-6 levels in the induction study and interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha levels in the treatment study. Our preliminary study is the first to show the anti-inflammatory effects of rosiglitazone in NASH. Rosiglitazone's effect on cytokines may be a key mechanism of its anti-inflammatory effect in NASH.Publication Metadata only Adenosine protects against indomethacin-induced gastric damage in rats(1998) YEGEN, BERRAK; Bozkurt, A.; Yüksel, M.; Haklar, G.; Kurtel, H.; Yeğen, B. C.; Alican, I.This study examines the putative gastroprotective effect of adenosine on indomethacin-induced gastric lesions and the possible mechanisms involved. After 24 hr of starvation, the rats were treated either with indomethacin (Indo; 25 mg/kg, subcutaneously) alone or adenosine + Indo (Ado; 7.5 mg/kg, subcutaneously, three times a day), or the vehicle (5% NaHCO3, subcutaneously). The length of hemorrhagic lesions in the stomachs was expressed as the lesion index. The tissue-associated myeloperoxidase (MPO) activity and protein oxidation were measured in gastric tissue samples. Formation of reactive oxygen species in gastric tissues was measured by using luminol- and lucigenin-enhanced chemiluminescence. In other groups of rats, gastric mucosal permeability and gastric acid output were performed following the same treatment regimens. The gastric mucosal permeability was measured by determination of [51Cr]EDTA clearance in a perfused stomach preparation and gastric acid secretion studies were performed following pylorus ligation. The lesion index, the increase in lucigenin-enhanced chemiluminescence, and the increase in gastric mucosal permeability in Indo-treated rats were reversed by Ado pretreatment. Ado pretreatment also prevented the increase in gastric acid output and gastric volume in Indo-treated rats. Thus, these findings implicate that exogenous adenosine has a protective role on indomethacin-induced gastric lesions, possibly by inhibiting gastric hyperacidity and reactive oxygen formation and by preventing disruption of the mucosal integrity.Publication Metadata only Role of ursodeoxycholic acid in prevention of methotrexate-induced liver toxicity(SPRINGER, 2008) ÇELİKEL, ÇİĞDEM; Uraz, Suleyman; Tahan, Veysel; Aygun, Cem; Eren, Fatih; Unluguzel, Goksenin; Yuksel, Meral; Senturk, Omer; Avsar, Erol; Haklar, Goncagul; Celikel, Cigdem; Hulagu, Sadettin; Tozun, NurdanAim Methotrexate (MTX)-induced hepatotoxicity restricts the clinical use of this immunosuppressive drug. In this study, our aim was to research the role of oxidative stress in the hepatic toxicity of MTX and the protective effect of ursodeoxycholic acid (UDCA) in this setting. Methods Wistar type rats (n = 32) were divided into four groups; group-1 as the MTX + UDCA, group-2 as the MTX, group-3 as the UDCA, group-4 as the saline-receiving groups. The MTX + UDCA and MTX groups of rats received 50 mg/kg of UDCA administered orally; whilst physiological saline was administered orally to the MTX and saline groups and continued for the next 6 days. On the second day of the study, the MTX + UDCA and MTX groups had a single intraperitoneal dose of MTX of 20 mg/kg. The UDCA and saline groups also received similar volumes of physiological saline intraperitoneally. On the sixth day, serum samples were collected and analyzed for ALT, alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) and homogenated liver tissues were examined for reactive oxygen metabolites (ROM); luminol, lucigenin, lipid peroxygenation product malondialdehyde (MDA) and glutathione (GSH) levels. Results In the MTX group, serum ALT, ALP, GGT and tissue ROM levels were higher and GSH level was lower. On the histopathological examination, hepatocellular necrosis was clearly more evident in the MTX group than the MTX + UDCA group. Conclusions UDCA treatment protects against MTX-induced liver toxicity. Histopathologically hepatocyte necrosis can be prevented by UDCA treatment, indicating clearly the hepatoprotective effect of this agent on MTX-induced liver injury.