Person: YEGEN, BERRAK
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YEGEN
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BERRAK
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Publication Open 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.Publication Metadata only Nesfatin-1 ameliorates oxidative bowel injury in rats with necrotizing enterocolitis: The role of the microbiota composition and claudin-3 expression(W B SAUNDERS CO-ELSEVIER INC, 2020) YEGEN, BERRAK; Cerit, Kivilcim Karadeniz; Koyuncuoglu, Turkan; Yagmur, Damla; Eyuboglu, Irem Peker; Sirvanci, Serap; Akkiprik, Mustafa; Aksu, Burak; Dagli, E. Tolga; Yegen, Berrak C.Background and Purpose: Ongoing high mortality due to necrotizing enterocolitis (NEC) necessitates the investigation of novel treatments to improve the outcome of the affected newborns. The aim was to elucidate the potential therapeutic impact of the nesfatin-1, a peptide with anti-inflammatory and anti-apoptotic effects in several inflammatory processes, on NEC-induced newborn rats. Materials and Methods: Sprague-Dawley pups were separated from their mothers, fed with a hyperosmolar formula and exposed to hypoxia, while control pups had no intervention. NEC-induced pups received saline or nesfatin-1 (0.2 mu g/kg/day) for 3 days, while some nesfatin-1 treated pups were injected with capsaicin (50 mu g/g) for the chemical ablation of afferent neurons. On the 4th day, clinical state and macroscopic gut assessments were made. In intestines, immunohistochemical staining of cycloxygenase-2 (COX-2), nuclear factor (NF)-kappa B-p65 (RelA), vascular endothelial growth factor (VEGF), claudin-3 and zonula occludens-1 (ZO-1) were performed, while gene expressions of COX-2, occludin, claudin-3, NF-kappa B-p65 (RelA) and VEGF were determined using q-PCR. In fecal samples, relative abundance of bacteria was quantified by q-PCR. Biochemical evaluation of oxidant/antioxidant parameters was performed in both intestinal and cerebral tissues. Results: Claudin-3 and ZO-1 immunoreactivity scores were significantly elevated in the nesfatin-1 treated control pups. Nesfatin-1 reduced NEC-induced high macroscopic and clinical scores, inhibited NF-kappa B-65 pathway and maintained the balance of oxidant/antioxidant systems. NEC increased the abundance of Proteobacteria with a concomitant reduction in Actinobacteria and Bacteroidetes, while nesfatin-1 treatment reversed these alterations. Modulatory effects of nesfatin-1 on microbiota and oxidative injury were partially reversed by capsaicin. Immunohistochemistry demonstrated that nesfatin-1 abolished NEC-induced reduction in claudin-3. Gene expressions of COX-2, NF-kappa B, occludin and claudin-3 were elevated in saline-treated NEC pups, while these up-regulated mRNA levels were not further altered in nesfatin-1-treated NEC pups. Conclusion: Nesfatin-1 could be regarded as a potential preventive agent for the treatment of NEC. (C) 2020 Elsevier Inc. All rights reserved.Publication Metadata only Nesfatin-1 treatment preserves antioxidant status and attenuates renal fibrosis in rats with unilateral ureteral obstruction(2022-06-01) ÇETİNEL, ŞULE; YEGEN, BERRAK; KAYA, ÖZLEM TUĞÇE; ÖZBEYLİ, DİLEK; Tezcan N., Özdemir-Kumral Z. N., Yenal N. Ö., Çilingir-Kaya Ö. T., Virlan A. T., Özbeyli D., Çetinel Ş., Yeğen B., Koç M.Background Nesfatin-1 (NES-1), an anorexigenic peptide, was reported to have anti-inflammatory and anti-apoptotic actions in several inflammation models. Methods To elucidate potential renoprotective effects of NES-1, unilateral ureteral obstruction (UUO) was induced in male Sprague Dawley rats by ligating left ureters. The rats were injected intraperitoneally with either saline (SL) or NES-1 (10 mu g/kg/day) for 7 or 14 days (n = 8 in each group). On the 7th or 14th day, obstructed kidneys were removed for the isolation of leucocytes for flow-cytometric analysis and the assessments of biochemical and histopathological changes. Results Opposite to glutathione levels, renal myeloperoxidase activity in the SL-treated UUO group was significantly increased compared with the sham-operated group, while NES-1 treatment abolished the elevation. The percentages of CD8+/CD4+ T-lymphocytes infiltrating the obstructed kidneys were increased in the SL-treated groups but treatment with NES-1 did not prevent lymphocyte infiltration. Elevated tumour necrosis factor-alpha (TNF-alpha) levels in SL-treated UUO group were decreased with NES-1. Although total degeneration scores were similarly increased in all UUO groups, tubular dilatation scores were significantly increased in UUO groups and lowered by NES-1 only in the 7-day treated group. Elevated interstitial fibrosis scores in the SL-treated groups were decreased in both 7- and 14-day NES-1 treated groups, while alpha-smooth muscle actin (alpha-SMA) and apoptosis scores were depressed in both NES-1 treated groups. Conclusion The present data demonstrate that UUO-induced renal fibrosis is ameliorated by NES-1, which appears to involve the inhibition of neutrophil infiltration and thereby amelioration of oxidative stress and inflammation. These data suggest that NES-1 may have a regulatory role in protecting the kidneys against obstruction-induced renal injury.Publication Open Access Peripheral administration of neuropeptide W inhibits gastric emptying in rats: the role of small diameter afferent fibers and cholecystokinin receptors(2023-02-10) YEGEN, BERRAK; Tamer S. A., Yeğen B.Neuropeptide W (NPW), a novel hypothalamic peptide, contributes to the central regulation of food intake and energy balance, and suppresses feeding behavior when administered centrally. The aim of our study was to investigate the role of peripherally administered NPW in the modulation of gastric emptying, and to evaluate the participation of afferent fibers, cholecystokinin (CCK) receptors and gastric smooth muscle contractility in the regulatory effects of NPW on gastric motility. In Sprague-Dawley male rats equipped with gastric fistula, gastric emptying rate of the saline and peptone solutions was measured following subcutaneous administration of NPW (0.1 or 5 μg/kg) preceded by subcutaneous injections of saline, CCK-1 or CCK-2 receptor antagonists. Another group of rats with cannulas were injected subcutaneously with capsaicin for afferent denervation before commencing emptying trials. The effect of NPW on carbachol-induced gastric contractility and the role of CCK receptors in gastric smooth muscle contractility were also assessed in gastric strips. Peripheral injection of NPW delayed gastric emptying rate of both caloric and non-caloric liquid test meals, while administration of CCK-1 or CCK-2 receptor antagonists or denervation of small diameter afferents reversed NPW–induced delay in gastric emptying. Moreover, NPW inhibited antrum contractility in the organ bath. Our results revealed that peripherally administered NPW delayed liquid emptying from the stomach via the involvement of small diameter afferent neurons and CCK receptors, and thereby this regulatory role may contribute to its central regulatory role in controlling food intake and energy balance.Publication Metadata only Interactions Of Estrogen And Oxytocin Receptors In Colonic Visceral Hypersensitivity Caused By Irritable Bowel Syndrome In Rats(2022-09-01) YILDIRIM, MUSTAFA AKİF; YEGEN, BERRAK; Kahraman M. M. , Mermer K. S. , Aksoy M. B. , Ozden L., Sakalli B. M. , Uludag A., Varol Y., YILDIRIM M. A. , YEGEN B.Publication Open Access The effects of resveratrol treatment on caveolin-3 expression and Na+/K+ ATPase activity in rats with isoproterenol-induced myocardial injury(KARE PUBL, 2020) YEGEN, BERRAK; Sehirli, Ahmet Ozer; Aykac, Asli; Tetik, Sermin; Yiginer, Omer; Cetinel, Sule; Ozkan, Naziye; Akkiprik, Mustafa; Kaya, Zehra; Yegen, Berrak Caglayan; Tezcan, Mehmet; Sener, GoekselOBJECTIVE: The present study aims to investigate the therapeutic effects of resveratrol (RES) on isoproterenol (ISO) induced myocardial injury rat model. METHODS: Catecholamine-induced heart damage was induced by ISO treatment for 30 days. The rats were divided into four groups as follows: the control group received saline, the ISO group received 5.0 mg/kg ISO, the RES group received 10 mg/kg RES, and the ISO-RES group received 10 mg/kg RES and 5 mg/kg ISO treatments for 30 days. Following echocardiographic measurements and body weight recorded, the rats were decapitated. Plasma and cardiac tissue samples obtained by decapitation were analyzed using biochemical, histopathological, molecular and immunohistochemical methods. RESULTS: In the ISO group, Na+/K+ ATPase activity and ATP content, GSH, and caveolin-3 levels were low. LDH, CK and lysosomal enzyme activities, MDA level, and MPO activity were found to be high. It was determined that GSH and MDA levels and MPO, Na+/K+ ATPase activity, ATP content caveolin-3 levels changes that arose from ISO treatment were suppressed by RES treatment. CONCLUSION: RES treatment has ameliorated all the functional and biochemical parameters. The results obtained in this study suggest that RES is a promising supplement against catecholamine exposure as it improves antioxidant defense mechanisms in the heart. In the light of above-mentioned data, RES can be assumed as a promising agent in ameliorating the oxidative injury of the myocardium.Publication Metadata only The ameliorative effects of melatonin on acetic acid-induced gastric ulcer in rats via its modulatory effects on gut microbiota(CUKUROVA UNIV, FAC MEDICINE, 2021) YILDIRIM, ALPER; Tamer, Sevil Arabaci; Yildirim, Alper; Cevik, Ozge; Aksu, Burak; Yuksel, Meral; Dertsiz, Ekin Kuntsal; Sirvanci, Serap; Yegen, Berrak C.Purpose: The aim of this study was of observe the possible protective effects of melatonin pretreatment on oxidative damage and microbiota alteration due to gastric ulcer in rats. Materials and Methods: Wistar-albino rats were given (n=32) melatonin (4 mg/kg/day), antibiotic mixture (AB; 1g/L ampicillin + 1g/L neomycin + 1g/L metronidazole), melatonin+AB in drinking water for 12 days or tap water for 15 days (control group; n=8). Subsequently, ulcer was induced. All treatments were continued for three days. Gastric tissues were obtained for biochemical and histopathological examinations, and fecal samples from the rectum were stored for bacteriological measurements. Results: MPO and MDA levels were increased in untreated ulcer groups compared to the control group. In addition, the levels of luminol-lucigenin chemiluminescence (CL) and 8-OHdG and TNF-alpha and IL-8 protein expressions were also increased, while TNF-alpha, IL-8, MDA, 8-OHdG, luminol and lucigenin CL levels were significantly decreased in the melatonin-treated ulcer groups. However, melatonin+AB pretreatment increased antioxidant GSH levels and anti-inflammatory IL-10 levels, and suppressed caspase-3 activity and reduced MPO back to control level. Conclusion: We anticipate that melatonin treatment, which is an effective antioxidant and radical scavenger, can accelerate ulcer healing along with antibiotics and increase the variety of bacteria impaired by antibiotics in the colon.Publication Open Access The potency of obestatin in improving kidney functions and apoptosis in rats with cisplatin-induced acute kidney injury(2022-01-01) ÖZDEMİR KUMRAL, ZARİFE NİGAR; BULUT, ALİSİNA; ÖZKAN YENAL, NAZİYE; YEGEN, BERRAK; KOÇ, MEHMET; ÖZDEMİR KUMRAL Z. N. , BULUT A., Üzülmez B., Vezirhüyük M., Kök Z., ÖZKAN YENAL N., YEGEN B., KOÇ M.© 2022 Marmara University Press.Cisplatin (CP), which is the most commonly used anticancer agent to treat several solid tumors, may cause acute kidney injury (AKI) as the major limiting factor for its clinical use. Obestatin (OB) is a ghrelin gene-derived peptide produced in several tissues and has shown anti-oxidant, anti-apoptotic, and anti-inflammatory effects in many experimental models. This study investigated the effect of OB treatment on nephrotoxicity induced by CP. Rats were divided into 4 groups as two control (1 ml/kg, saline, intraperitoneal (ip), single dose) and two CP-induced (7 mg/kg, ip, single dose) AKI groups (8 rats in each group). Immediately after the CP injection and the following two days, injections of OB (10 µg/kg, ip) were performed. Rats were decapitated at the end of 72 hours. Blood and kidney tissue samples were taken for biochemical and histopathological measurements. The results of the present study revealed that serum creatinine and BUN levels were significantly increased in the CP-induced AKI group when compared to the control group. Treatment with OB improved kidney functions and ameliorated renal oxidative injury and maintained oxidative balance in the CP-induced AKI model, which was revealed by elevated malondialdehyde and depleted glutathione levels. TUNEL scores also demonstrated that CP increased the apoptotic response, while OB treatment abolished it. CP-induced medullary and cortical injuries were also partially reversed by OB treatment. Thus, our findings show that OB alleviates CP-induced nephrotoxicity in rats through the abolishment of oxidative stress and apoptosis.Publication Open 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 inhibitorPublication Open 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.