Browsing by Author "Bayçu, Cengiz"
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Article Citation Count: 8Beneficial effect of mirtazapine on diabetes-induced hyperalgesia: involvement of TRPV1 and ASIC1 channels in the spinal cord and dorsal root ganglion(Taylor & Francis Ltd, 2019) Bektur, Ezgi; Sahin, Erhan; Ceyhan, Emre; Donmez, Dilek Burukoglu; Canbek, Mediha; Baycu, Cengiz; Can, Ozgur Devrim; Histoloji ve Embriyoloji / Histology and EmbriologyObjectives: Neuropathic pain reduces the life qualities of patients with Diabetes mellitus. Clinical guidelines recommend relief in diabetic neuropathic pain through the use of some antidepressants, anticonvulsants, opioids as well as capsaicin cream or lidocaine patches. However, since the majority of patients do not or partially respond to current treatments, there is a growing necessity for new drugs increasing the pain relief in patients with diabetes. Therefore, based on the therapeutic potential of antidepressants on neuropathic pain, we investigated the promising antihyperalgesic effect of mirtazapine (MRT) in painful diabetic neuropathy. Methods: Experimental diabetes was induced in rats by single intraperitoneal injection of 55 mg/kg dose of streptozocin (STZ). After 4 weeks of injection of STZ, MRT was administrated for 14 days at 40 mg/kg dose. Randall-Selitto and Hargreaves tests were applied for paw-withdrawal threshold and paw-withdrawal latency measurement. TRPV1 and ASIC1 expressions measured by Western blot in dorsal root ganglion and spinal cord. Results: Administration of MRT significantly improved both of the decreased paw-withdrawal threshold and shortened the paw-withdrawal latency of diabetic rats, respectively. Besides, increased levels of TRPV1 and ASIC1 channels in dorsal root ganglion and spinal cord of diabetic rats, evaluated by Western blot method, were decreased following the MRT treatment. Discussion: These data show, for the first time, that MRT has beneficial effects against diabetes-induced hyperalgesia, and that suppressive effect of this drug on TRPV1 and ASIC1 levels, which are increased in diabetic rats, may be some of the pharmacological mechanisms underlying the exhibited antihyperalgesic effect of MRT.Article Citation Count: 9Hippocampal neural cell loss in high-fat diet-induced obese rats-exploring the protein networks, ultrastructure, biochemical and bioinformatical markers(Elsevier, 2021) Alkan, Isinsu; Altunkaynak, Berrin Zuhal; Gultekin, Guldal Inal; Baycu, Cengiz; Histoloji ve Embriyoloji / Histology and Embriology; Fizyoloji / PhysiologyObjective: Obesity, which has become one of the main health problems, results from irregular and unhealthy nutrition. In particular, an increase in the intake of high-fat foods leads to obesity and associated disorders. It is noteworthy to specify that obese individuals have memory problems. This study aims to examine the effects of high-fat diet on hippocampus, with stereological, histopathological methods and STRING bioinformatic tool. Methods: Female Adult Sprague Dawley rats (n = 20) were equally divided into control (CONT) and high-fat diet (HFD) groups. The control group was given standard rat pellet feed, while the high-fat diet group was fed with a 40 % fat content for 2 months. Following the feeding program, rats were sacrificed. The collected blood samples were analyzed biochemically to determine the level of oxidative stress while performing a stereological and histopathological examination of the brain tissues. Functional protein-protein networks for BDNF, C-Fos, CAT, LPO, SOD and MPO by gene ontology (GO) enrichment analysis were evaluated. Findings: The number of neurons decreased in the HFD group compared to the CONT group. Damage to the histological structure of the hippocampus region; such as degenerate neurons, damaged mitochondria and extended cisterns of the endoplasmic reticulum was observed. Although C-Fos level and oxidative stress parameters increased in HFD group, BDNF level decreased. While BDNF and C-Fos were observed in pathways related to neuron death, oxidative stress and memory, BDNF was pronounced in the mitochondria, and C-Fos in the endoplasmic reticulum. Discussion: This study shows that changes in both BDNF and C-Fos levels in obesity due to high-fat diet increase oxidative stress and cause neuron damage in the hippocampus.Article Citation Count: 9HYPOTHYROIDISM INCREASES EXPRESSION OF STERILE INFLAMMATION PROTEINS IN RAT HEART TISSUE(Editura Acad Romane, 2019) Sahin, E.; Bektur, E.; Baycu, C.; Donmez, D. Burukoglu; Kaygisiz, B.; Histoloji ve Embriyoloji / Histology and EmbriologyPurpose. In this study, we aimed to investigate the relationship between hypothyroidism and sterile inflammation in rat heart tissue. Methods. Groups; control group (fed with standard rat chow diet and tab water) and the hypothyroid group (fed with a standard rat chow diet and tap water containing 0.05% 6-n-propyl-2-thiouracil for 6-weeks). At the end of the experiment, histopathologic examination was performed. The T3, T4, TSH and myocardial malondialdehyde (MDA) measurements were performed with an ELISA kit. TUNEL assay was performed to demonstrate apoptosis. Sterile inflammation markers, caspase-1 and NLRP3, were investigated by immunohistochemistry and western blot. Results. In histopathological examination, we observed leukocyte infiltration, myocardial atrophy, pyknotic nucleated cells and cytoplasmic vacuolization in hypothyroid group whereas the control group showed normal structure. MDA levels in myocardial tissue were significantly high in hypothyroid group when compared to the control group (P<0.05). Myocardial apoptosis increased in hypothyroid group when compared to the control group. NLRP3 and caspase-1 immunoreactivity was higher in the hypothyroid group. In ELISA results, we found significantly higher level of TSH and lower levels of T3 and T4 in hypothyroid group when compared to the control group. Conclusion. Hypothyroidism increased oxidative stress, and caused inflammatory alterations in cardiac tissue. In addition, our study also suggested that thyroid hormone deficiency would increase the amounts of cardiac NLRP3 and caspase-1 protein, which indicates that hypothyroidism exerts its destructive effects through sterile inflammation. Elucidation of sterile inflammation-associated pathways may produce promising results in the treatment of hypothyroidism-induced cardiac damage.Article Citation Count: 0Mirtazapin Diyabet Oluşturulan Sıçanların Beyinciklerindeki Hasarı Kısmen Düzeltmektedir(2018) Özgür Devrim CAN; Dilek Burukoğlu DÖNMEZ; Varol ŞAHİNTÜRK; NURİYE EZGİ BEKTUR AYKANAT; Erhan ŞAHİN; Cengiz BAYÇU; Histoloji ve Embriyoloji / Histology and EmbriologyDiabetes mellitus (DM) sistemik bir hastalık olup çeşitli organlarda hasara neden olmaktadır. Bu organlar arasında beyincikde yer almaktadır. Mirtazapin ise majör depresyon tedavisinde kullanılan bir antidepresan madde olup inflamasyon yanıtınındüzenlenmesinde de rol oynamaktadır. Bütün bu bilgiler ışığında, çalışmamızda DM oluşturulan sıçanların beyinciklerindemeydana gelen değişiklikleri ve bu değişiklikler üzerine mirtazapinin etkilerini araştırmayı amaçladık. Çalışmamızda toplam 21 adetyetişkin, erkek Sprague Dawley sıçan 3 eşit gruba ayrıldı (n=7). Kontrol grubuna hiçbir uygulama yapılmadı. DM grubundakihayvanlara tek doz 55 mg/kg streptozotosin intraperitoneal olarak verilerek DM oluşturuldu. Mirtazapin grubuna streptozotosinuygulamasından 28 gün sonra, 14 gün boyunca günde 20 mg/kg mirtazapin gavaj yoluyla uygulandı. Deney sonunda alınan beyincikörnekleri %10’luk formaldehit ile fikse edildikten sonra rutin doku takip işleminin ardından alınan kesitlere hematoksilen ve eozin,krezil viyole boyama teknikleri ve akson rejenerasyonunu belirlemek amacıyla da GAP-43 immünohistokimyasal boyamasıuygulandı. Kontrol grubunda beyincikte normal histoloji ile medüllada yüksek GAP-43 ekspresyonu gözlendi. DM grubundaPurkinje nöronlarında büzüşme ve bazı alanlarda hücre ölümü saptanırken, orta düzeyde GAP-43 immünoreaksiyonu belirlendi.Mirtazapin uygulanan grupta ise Purkinje nöronlarının ve histolojik yapının kontrol grubuna yakın olduğu gözlenirken GAP-43ekspresyonunun DM grubuna benzer olduğu saptandı. Sonuç olarak, streptozotosinle oluşturulan DM sıçanların beyinciğindeözellikle Purkinje nöronlarında hasara ve medüllada miyelin kaybına yol açmakta ve mirtazapin uygulaması Purkinje nöronlarındakihasarı azaltmakta, ancak miyelin rejenerasyonunu sağlamada belirgin bir etki göstermemektedir.Article Citation Count: 7Mirtazapine may show anti-hyperglycemic effect by decreasing GLUT2 through leptin and galanin expressions in the liver of type 1 diabetic rats(Mashhad Univ Med Sciences, 2019) Bektur, Ezgi; Sahin, Erhan; Baycu, Cengiz; Histoloji ve Embriyoloji / Histology and EmbriologyObjective(s): The aim of this study was to explore the molecular mechanism of mirtazapine with respect to energy metabolism in Streptozotocin-induced diabetic liver of rats by immunohistochemictry and Western blot. Materials and Methods: Twenty-one male Sprague-Dawley rats were assigned into 3 groups including control, type 1 diabetes mellitus (T1DM) group (55 mg/kg Streptozocin, IP) and T1DM+mirtazapine (20 mg/kg, PO) group. At the end of the experiment, blood glucose levels were measured and liver tissues were stained by Periodic acid-Schiff. Moreover, leptin and glucose transporter 2 (GLUT2) proteins were analyzed by western blot and immunohistochemistry; however, galanin were analyzed only by immunohistochemistry. Results: At the end of the study, in diabetes group, blood glucose level, GLUT2 and galanin expressions increased, while leptin expression decreased when compared to control group. Mirtazapine treatment restored the decreased leptin expression, and the increased blood glucose level and galanine expression to the level of the control group. It also decreased the GLUT2 expression even below the control group. Conclusion: We concluded that mirtazapine may show its anti-hyperglycemic effect by decreasing GLUT2 through altering the leptin and galanin expression in the liver of type 1 diabetic rats. Mirtazapine can be used as an antidepressant for T1DM patients and as a drug to reduce blood glucose level in T1DM.Article Citation Count: 15Mirtazapine suppresses sterile inflammation through NLRP3-inflammasome in diabetic rat kidney(Elsevier Gmbh, 2019) Sahin, Erhan; Bektur, Ezgi; Donmez, Dilek Burukoglu; Baycu, Cengiz; Can, Ozgur Devrim; Sahinturk, Varol; Histoloji ve Embriyoloji / Histology and EmbriologyAim The aim of this study was to investigate the effects of mirtazapine, which is anti-oxidative and antidepressant agent, on the kidney damage caused by diabetes mellitus. Materials and methods: The rats were randomly divided into three groups (n = 7 animals in each group). The group I rats served as control and they received 0.1 mol/L of citric acid buffer (pH = 4.5) as vehicle. The rats in the group II (DM group) and III (DM + Mirtazapine-treated group) were treated intraperitoneally with a single dose of 55 mg/kg streptozotocin dissolved in 0.1 mol/L of citric acid buffer. Group DI rats were also received 20 mg/kg/day of mirtazapine for 2 weeks. At the end of the experiment, the rats were sacrificed. Then, the kidneys were excised and prepared for microscopical examination, caspase-1 and NLRP3 proteins were examined using immunohistochemistry and western blotting. The TUNEL assay for apoptosis and ELLSA assay for IL-1 beta were performed. Results: Histological examination showed that mirtazapine administration has an ameliorative effect on DM-induced kidney damage. Immunohistochemical and western blot analyses showed that NLRP3 and caspase-1 expressions were increased in the DM group according to the control group and the mirtazapine administration decreased these expressions. The intraglomerular and tubular TUNEL-positive cells were numerous in the DM group compared to the mirtazapine-treated group. The level of IL-1 beta was highest in the DM group, and decreased significantly in the mirtazapine-treated group. Conclusion: In this study, 20 mg/kg/day mirtazapine administration for 2 weeks reduced NLRP3 and caspase-1 expressions and IL-1 beta level in the diabetic rat kidneys. These results suggesting that mirtazapine may be useful in the treatment of DM and other metabolic diseases. Advanced molecular studies are needed to elucidate the exact effects of mirtazapine on NLRP3 inflammasome.Article Citation Count: 0TİP 1 DİYABETES MELLİTUS OLUŞTURULAN SIÇANLARIN BEYNİNDE LEPTİN MİKTARI AZALMAKTADIR(2019) Demir, Ümide Özkay; Can, Özgür Devrim; Özcan, Öykü; Sahın, Erhan; Şahintürk, Varol; Bektur, Ezgi; Bayçu, Cengiz; Histoloji ve Embriyoloji / Histology and EmbriologyAMAÇ: Leptin hormonu, iştah ve vücut metabolizması-nın düzenlenmesinde önemli görevler üstlenmekte vebaşlıca yağ dokusunda sentezlenmektedir. Leptinin yağdokuda sentezlendikten sonra koroid pleksus aracılığı ilebeyne taşındığı bilinmektedir. Bu çalışmanın amacı Tip 1diyabetes mellitus oluşturulan sıçanların beyninde leptinifadesinin ve miktarının araştırılmasıdır.GEREÇ VE YÖNTEM: Çalışmamızda toplam 14 adet yetiş-kin, erkek Wistar Albino sıçan 2 eşit gruba ayrıldı (n=7).Kontrol grubuna hiçbir uygulama yapılmadı. Diyabetesmellitus grubundaki hayvanlara ise tek doz (55 mg/kg)streptozotosin intraperitoneal olarak verildi ve kan glukozseviyesi >280 mg/dL ölçüldüğünde Tip 1diyabetes mellitus geliştiği kabul edildi. Deney sonunda alınan beyinörnekleri %10’luk formaldehit ile fikse edildikten sonrarutin doku takip işleminin ardından alınan kesitlere leptinimmünohistokimyasal boyaması uygulandı. Beyin dokularında western blot yöntemi ile leptin miktarına bakıldı.BULGULAR: Tüm gruplara ait beyin kesitlerinde sadecekoroid pleksusta leptin boyanması saptandı. Buna göre,leptin boyanmasının Tip 1 diyabetes mellitus geliştirilensıçanlarda azaldığı saptandı. Western blot ile Tip 1diyabetes mellitus grubunda leptin miktarının belirginolarak azaldığı saptandı.SONUÇ: Bu çalışmayla tokluk hissini oluşturmaküzere koroid pleksus üzerinden beyne geçen leptin hormonu ile diyabet arasında yakın bir ilişki olduğu ve bu hormonun diyabetle azaldığı gösterilmiştir. Bu çalışmadan yola çıkarak Tip 1 diyabet veleptin hormonu ilişkisi derinlemesine irdelenmelidir.