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YEGEN, BERRAK

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Author: ERCAN, FERİHA × Has files: true ×

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    PublicationOpen Access
    Ghrelin Treatment Improves Lipid Metabolism and Hepatic Degeneration in Ovariectomized Rats
    (GAZI UNIV, FAC MED, 2020-01-01) YEGEN, BERRAK; Gurler, Esra Bihter; Ozbeyli, Dilek; Kaya, Ozlem Tugce Cilingir; Ercan, Feriha; Yegen, Berrak C.
    Objective: Metabolic disorders occurring in post-menopausal period increase the risk for development of fatty liver disease in women. Aim of the study was to evaluate possible effects of ghrelin on metabolic biomarkers and hepatic morphology in ovariectomized (OVT) rats. Methods:Under ketamine-chlorpromazine anesthesia (100 mg/kg, 0.75 mg/kg), Sprague-Dawley rats (n=12) underwent bilateral OVT, while control group had sham-surgery (n=6). Four weeks after surgery, half of OVT rats were treated intraperitonally with ghrelin (1 mg/kg/hafta) for 4 weeks, while others were not treated. Rats were euthanized by cardiac puncture at the end of 8th weeks, and serum levels of glucose, insulin, aspartate aminotransferase (AST), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), triglycerides, estradiol and progesterone were measured by an automated analyzer. Results: Increased body weights in OVT rats (p<0.001) recorded at the end of 2 months was not changed with ghrelin. Serum estradiol and progesterone levels were reduced (p<0.05) verifying altered gonadal hormone status, but insulin and glucose levels were not changed. Reduced HDL and increased LDL levels (p<0.0.5) were evident in non-treated OVX rats, while ghrelin treatment depressed LDL levels (p<0.0.5), but did not change HDL levels. However, ghrelin in OVT rats depressed triglycerides, VLDL and AST levels significantly (p<0.05). Moderate sinusoidal congestion, activated Kupffer cells and hepatocytes with ballooning degeneration was observed in non-treated OVT rats, while significant improvements were present in livers of ghrelin-treated rats. Conclusion: In conclusion, mild dyslipidemia and hepatic degeneration in early post-menopausal period appear to be attenuated by ghrelin treatment, and require further investigation.
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    PublicationOpen Access
    Neuropeptide w alleviates hepatorenal oxidative damage in sepsis-induced rats
    (2020-05-01) ATICI, ALİ EMRE; PEKER EYÜBOĞLU, İREM; ERCAN, FERİHA; AKKİPRİK, MUSTAFA; YEGEN, BERRAK; ATICI A. E., ARABACI TAMER S., levent h. n., PEKER EYÜBOĞLU İ., ERCAN F., AKKİPRİK M., YEGEN B.
    Background: Despite modern surgical, medical and intensive care treatments, sepsis is still one of the most frequent causes of morbidity and mortality due to multiple life-threatening organ dysfunctions. We aimed to investigate the possible protective effect of neuropeptide W (NPW), a novel peptide effective in regulating neuroendocrine functions, against sepsisinduced hepatorenal damage. Methods: In male Sprague-Dawley rats (200–250 g), sepsis was induced by cecal ligation and puncture under ketamine anesthesia (n=48). Immediately after surgery, saline or TNF-alpha inhibitor (etanercept; 1 mg/kg) plus antibiotic (ceftriaxon; 100 mg/kg) (ET+C) or NPW (0.1, 0.3, 1 or 3 mg/kg) was given subcutaneously, and repeated at 12th and 24th hours, while sham-operated control group (n=8) received three saline injections within twenty-four hours. Rats were decapitated at the 25th hour of surgery and C-reactive protein (CRP), corticosterone and IL-6 levels were measured in serum samples. Kidney and liver samples were obtained for the measurement of myeloperoxidase activity (MPO), malondialdehyde and glutathione levels and nuclear factor kappa-B (NF-kB) mRNA expression levels. Histopathological evaluations were performed in hematoxylin-eosin-stained samples. ANOVA and Student's t-tests were used for data analysis. Results: Elevated serum levels of IL-6, corticosterone and CRP (p<0.05-0.01) in saline-treated sepsis group, as compared to controls, were depressed in the ET+C- (p<0.05) or NPW- (p<0.05-0.001) treated groups. Hepatic malondialdehyde and MPO levels, which were increased in salinetreated sepsis group (p<0.05 and p<0.001), were decreased by ET+C- (p<0.01) or NPW (p<0.05-0.001) treatments. Similarly, increased renal malondialdehyde level was depressed by NPW (p<0.05), but not by ET+C; while none of the treatments had an inhibitory effect on renal MPO. In contrast to replenished renal glutathione levels by all treatments, hepatic glutathione content was not changed by any of the treatments. Hepatic and renal NF-kB mRNA expressions were similar in all groups. Severe hepatocyte degeneration, sinusoidal congestion and inflammatory cell infiltration were observed in saline-treated sepsis group, while parenchymal degeneration, congestion and Kupffer cell activation were mild in ET+Cand NPW-treated sepsis groups. Similarly, severe degeneration of renal corpuscles and tubules with glomerular and interstitial congestion in the saline-treated sepsis group was replaced by moderate glomerular and interstitial vascular congestion and mild tubular congestion in both NPW- and ET+C-treated groups. Conclusion: NPW, applied during the first 24 hours of sepsis, exerted a dose-dependent protective effect against hepatorenal damage, which appears to involve an inhibitor
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    PublicationOpen Access
    Cerrahi menopoz oluşturulmuş sıçanların karaciğer ve böbrek dokularında oksidan/antioksidan dengenin korunmasında egzersizin ve östrojenin yararlı etkileri
    (2022-09-01) YÜKSEL, MERAL; ERCAN, FERİHA; YILDIRIM, ALPER; YEGEN, BERRAK; Tamer S. A. , Levent N., Yüksel M., Ercan F., Yıldırım A., Yegen B.
    Amaç: Bu çalışmanın amacı cerrahi olarak menopoz oluşturulan sıçanların böbrek ve karaciğerlerinde gözlenen histopatolojik ve fonksiyonel değişiklikleri ve östrojen veya egzersizin ya da östrojen-egzersiz kombinasyonunun oksidan hasar üzerine etkilerini araştırmaktır.Materyal ve Metot: Anestezi altında Sprague Dawley dişi sıçanlara (n=32) bilateral overiektomi uygulandı ve tüm sıçanlar rastgele olarak iki gruba ayrıldı. Sıçanların yarısına normal içme suyu, diğer yarısının içme sularına östrojen (1mg/kg/gün) eklendi. İki hafta sonra gruplar kendi içlerinde sedanter ve egzersiz (5 gün/hafta, 30 daki-ka, 8 hafta) gruplarına ayrıldı. Deney protokolünün sonun-da serum, karaciğer ve böbrek örnekleri biyokimyasal ve histopatolojik incelemeler için alındı. Femurda da histopa-tolojik değerlendirme yapıldı.Bulgular: Cerrahi olarak menopoz oluşturulan sıçan-larda östrojenin böbrek dokusunda nötrofil infiltrasyonunu ve reaktif oksijen türlerinin üretimini baskılayarak koruyu-cu etki gösterdiği, kemik kütlesinde hafif düzeyde artışa neden olduğu, ancak karaciğerin antioksidan glutatyon düzeyinde azalmaya yol açtığı belirlenmiştir. Buna karşın, östrojen uygulaması menopozda yapılan egzersiz nedeniy-le karaciğerde oluşan oksidan stresi engellemiştir. Egzer-sizle veya egzersize östrojen tedavisinin eklenmesiyle böbrek fonksiyonları önemli ölçüde etkilenmezken, kemik yapısında tek başına östrojene kıyasla daha olumlu deği-şiklikler gözlenmiştir.Sonuç: Östrojen replasmanı kemik dokusundaki olum-lu etkilerinin yanı sıra karaciğer ve böbrekte oksidan stresi azaltmakta ve özellikle karaciğerde egzersize bağlı gelişen oksidan stresi baskılayarak koruyucu etki göstermektedir.
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    PublicationOpen Access
    Nikotinin Sıçan Pankreatit_x000D_ Modelindeki Hafifletici Etkisinde_x000D_ Vagusun Rolünün Araştırılması
    (2021-04-01) YEGEN, BERRAK; Meltem KOLGAZİ;Zozan GÜLEKEN;Bircan KOLBAŞI;Canberk Sami BAŞIBÜYÜK;Feriha ERCAN;Berrak Çağlayan YEĞEN
    Nikotinin birçok farklı dokuda anti-inflamatuvar etkilere sahip olduğu ve bu etkileri kolinerjik anti-inflamatuvar yolağı aktive_x000D_ ederek gerçekleştirdiği gösterilmiştir. Çalışmada akut pankreatit modelinde nikotin tedavisinin etkilerini ve bu etkilerin_x000D_ kolinerjik yolla ilişkisini araştırmak amaçlanmıştır. Wistar albino sıçanların pankreas-safra ortak kanalı bağlanırken (PSKB),bir_x000D_ gruba da yalancı-cerrahi (YC) uygulandı. PSKB sıçanlara vagal aferent denervasyon (perivagal kapsaisin; 10mg/ml) veya_x000D_ trunkal vagotomi uygulandı ya da vagusları sağlam bırakıldı. PSKB grupları cerrahi sonrası ikiye ayrılarak 4 gün boyunca_x000D_ intraperitoneal nikotin (1 mg/kg/gün) ya da serum fizyolojik verildi. Dördüncü günde dekapitasyonu takiben, serumda tümör_x000D_ nekroz faktör (TNF)-∝ ve interlökin (IL)-10 ölçümü, akciğer, karaciğer ve pankreas dokularında miyeloperoksidaz aktivitesi_x000D_ (MPO), malondialdehit (MDA), glutatyon (GSH) ölçümleri ve histolojik inceleme yapıldı. TNF-∝ düzeyi PSKB grubunda YC_x000D_ grubuna göre belirgin şekilde daha yüksekken, nikotin tedavisi alanlarda belirgin şekilde daha düşüktü. IL-10 düzeyi ise SF_x000D_ tedavisi almış PSKB grubunda YC grubuna göre daha düşüktü ve nikotin tedavisi ile arttığı gözlendi.YC grubuna göre PSKB_x000D_ grubunun pankreas, karaciğer ve akciğer dokularında mikroskopik hasar, MDA, MPO düzeyleri artarken GSH düzeyleri azaldı._x000D_ Nikotin tedavisi ile karaciğer ve pankreas dokularındaki hasar, MDA, MPO düzeyleri azaldı ve GSH miktarları korundu. Vagal_x000D_ aferent denervasyon ya da trunkal vagotomi yapılması nikotinin bu koruyucu etkilerini değiştirmedi. Sonuçlar, nikotinin_x000D_ pankreatit hasarına karşı koruyucu etkilerini vagal yoldan bağımsız olarak, doğrudan immün hücreler üzerindeki ∝7nAChR_x000D_ aktivasyonu ile nötrofil infiltrasyonunu ve pro-inflamatuvar sitokinleri inhibe ederek gerçekleştirdiğini ortaya koymaktadır._x000D_ _x000D_ Anahtar Kelimeler: pankreatit, nikotin, vagus, inflamasyon, pankreatik kanal bağlama
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    PublicationOpen Access
    Neuropeptide W Exhibits Preventive and Therapeutic Effects on Acetic Acid-Induced Colitis via Modulation of the Cyclooxygenase Enzyme System
    (2023-01-01) ARABACI TAMER, SEVİL; ERCAN, FERİHA; YEGEN, BERRAK; ARABACI TAMER S., Akbulut S., Erdogan O., Cevik O., ERCAN F., YEGEN B.
    Background The novel peptide neuropeptide W (NPW) was originally shown to function in the control of feeding behavior and energy homeostasis. The aim of this study was to elucidate the putative preventive and therapeutic effects of NPW on colitis-associated oxidative injury and the underlying mechanisms for its action.Methods Sprague-Dawley rats in the acute colitis groups received NPW (0.5, 1 or 5 mu g/kg/day) injections prior to induction of colitis with acetic acid, while the chronic colitis groups were treated after the induction of colitis. In both acute and chronic colitis (CC) groups, treatments were continued for 5 days and the rats were decapitated at the 24th hour of the last injections and colon tissues were collected for assessments.Results NPW pretreatment given for 5 days before colitis induction, as well as treating rats with NPW during the 5-day course of CC, abolished colonic lipid peroxidation. NPW treatment prevented colitis-induced reduction in blood flow, diminished neutrophil infiltration, and pro-inflammatory cytokine responses. NPW pretreatment only at the higher dose reduced colonic edema and microscopic score and preserved colonic glutathione stores. Elevations in cyclooxygenase (COX) enzyme activity and COX-1 protein level during the acute phase of colitis as well as reduction in COX-2 were all reversed with NPW pretreatment. In contrast, NPW treatment was effective in reducing the elevated COX-2 concentration during the chronic phase.Conclusions NPW alleviates acetic acid-induced oxidative colonic injury in rats through the upregulation of colonic blood flow as well as the inhibition of COX-2 protein expression and pro-inflammatory cytokine production.
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    PublicationOpen Access
    Melatonin alleviates ovariectomy-induced cardiovascular inflammation in sedentary or exercised rats by upregulating SIRT1
    (2022-12-01) ERCAN, FERİHA; YILDIRIM, ALPER; YEGEN, BERRAK; Arabacı Tamer S., Altınoluk T., Emran M., Korkmaz S., Yüksel R. G., Baykal Z., Dur Z. S., Levent H. N., Ural M. A., Yüksel M., et al.
    © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.We aimed to evaluate the impact of hormone replacement, melatonin, or exercise alone or their combination on oxidative damage and functional status of heart, brain, and aorta of ovariectomized (OVX) rats and to determine whether the signaling pathway is dependent on sirtuin-1 (SIRT1). Ovariectomized Sprague Dawley rats were orally given either a hormone replacement therapy (1 mg/kg/day,17β estradiol; HRT) or melatonin (4 mg/kg/day) or HRT + melatonin treatments or tap water, while each group was further divided into sedentary and exercise (30 min/5 days/week) groups. After the heart rate measurements and memory tests were performed, trunk blood was collected at the end of the 10th week to determine metabolic parameters in serum samples. Tissue samples of abdominal aorta, heart, and brain were taken for biochemical measurements and histopathological evaluation. Heart rates and memory performances of the OVX rats were not changed significantly by none of the applications. Melatonin treatment or its co-administration with HRT upregulated the expressions of IL-10 and SIRT1, reduced the expressions of IL-6 and TNF-α, and reduced DNA damage in the hearts and thoracic aortae of non-exercised rats. Co-administration of melatonin and HRT to exercised OVX rats reduced inflammatory response and upregulated SIRT1 expression in the aortic and cardiac tissues. The present study suggests that melatonin treatment, either alone or in combination with exercise and/or HRT, upregulates SIRT1 expression and alleviates oxidative injury and inflammation in the hearts and aortas of OVX rats. Melatonin should be considered in alleviating cardiovascular disease risk in postmenopausal women.
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    PublicationOpen Access
    Colitis-induced oxidative damage of the colon and skeletal muscle is ameliorated by regular exercise in rats: the anxiolytic role of exercise
    (WILEY, 2006-09-01) YEGEN, BERRAK; Kasimay, Ozgur; Guzel, Esra; Gemici, Ali; Abdyli, Asead; Sulovari, Admir; Ercan, Feriha; Yegen, Berrak C.
    Epidemiological studies have shown that exercise protects the gastrointestinal tract, reducing the risk of diverticulosis, gastrointestinal haemorrhage and inflammatory bowel disease, while many digestive complaints occurring during exercise are attributed to the adverse effects of exercise on the colon. In order to assess the effects of regular exercise on the pathogenesis of colitis, Sprague-Dawley rats of both sexes were either kept sedentary or given exercise on a running wheel (0.4 km h(-1), 30 min for 3 days week(-1)). At the end of 6 weeks, under anaesthesia, either saline or acetic acid (4%, 1 ml) was given intracolonically. Holeboard tests were performed for the evaluation of anxiety at 24 h before and 48 h after induction of colitis. Increased 'freezing time' in the colitis-induced sedentary group, representing increased anxiety, was reduced in the exercised colitis group (P < 0.05). On the third day following the colonic instillation, the rats were decapitated under brief ether anesthesia and the distal 8 cm of the colons were removed. In the sedentary colitis group, macroscopic and microscopic damage scores, malondialdehyde level and myeloperoxidase activity were increased when compared to the control group (P < 0.01-0.001), while exercise prior to colitis reduced all the measurements with respect to sedentary colitis group (P < 0.05-0.001). The results demonstrate that low-intensity, repetitive exercise protects against oxidative colonic injury, and that this appears to involve the anxiolytic effect of exercise, suggesting that exercise may have a therapeutic value in reducing stress-related exacerbation of colitis.
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    PublicationOpen Access
    Neuropeptide W Attenuates Oxidative Multi-Organ Injury in Rats Induced with Intra-Abdominal Sepsis
    (SPRINGER/PLENUM PUBLISHERS, 2022-02) YEGEN, BERRAK; Atici, Ali Emre; Tamer, Sevil Arabaci; Levent, Hilal Nisva; Eyuboglu, Irem Peker; Ercan, Feriha; Akkiprik, Mustafa; Yegen, Berrak C.
    Sepsis leads to systemic hypotension, disturbed perfusion, inflammation, and tissue toxicity in vital organs. Neuropeptide W (NPW) has modulatory effects in the control of blood pressure and inflammatory processes, implicating a potential beneficial effect against sepsis-induced oxidative damage. Under anesthesia, male Sprague Dawley rats underwent cecal ligation and puncture. Immediately after surgery, either saline or TNF-alpha inhibitor (etanercept; 1 mg/kg) antibiotic (ceftriaxon; 10 mg/kg) combination or NPW (0.1, 1, or 3 mu g/kg) was given subcutaneously, and injections were repeated on the 12th and 24th h. The sham-operated control group was treated with saline at the same time points. All rats were euthanized on the 25th h of surgery. Sepsis resulted in oxidative damage of the brain, heart, lung, liver, and kidney. Elevations in blood urea nitrogen and alkaline phosphatase, showing renal and hepatic dysfunction, were not evident when septic rats were treated with NPW. NPW reduced serum levels of C-reactive protein, corticosterone, and interleukin-6, while histopathologically verified tissue damage in all the studied tissues was ameliorated. NPW treatment suppressed lipid peroxidation in the heart, lung, and brain, and the depleted antioxidant GSH levels of the brain and heart were replenished by NPW. Moreover, sepsis-related neutrophil recruitment to the liver and lung was also suppressed by NPW. Although the survival rate of the rats was not significantly prolonged by NPW, most of these improvements in systemic and local inflammatory events were comparable with those reached by the etanercept and antibiotic combination, suggesting the therapeutic impact of NPW during the acute period of sepsis.