Person: YEGEN, BERRAK
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YEGEN
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BERRAK
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Publication Metadata only Bombesin ameliorates colonic damage in experimental colitis(1999) YEGEN, BERRAK; Güllüoğlu, B. M.; Kurtel, H.; Güllüoğlu, M. G.; Aktan, A. O.; Yeğen, B. C.; Dizdaroğlu, F.; Yalin, R.; Yeğen, B. C.In the present study we investigated the possible therapeutic effects of bombesin on an experimentally induced colitis model in rats. Inflammation of the colon was induced by a single intracolonic administration of 30 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS) at 8 cm from the anus. Immediately after the induction of colitis, some rats were given bombesin (10 microg/kg; subcutaneously) three times a day for 14 days, while another group received vehicle treatment. On day 14, the rats were decapitated and plasma carbonyl content and tissue myeloperoxidase level, as an index of granulocyte infiltration into intestinal tissue, were determined in order to obtain an objective evaluation of colonic injury. In the colitis group, increased macroscopic damage score, elevated MPO level and high plasma carbonyl content, together with the microscopic appearance revealed severe inflammatory changes resembling IBD. Bombesin treatment attenuated the TNBS-induced colonic damage and stimulated histopathologically apparent mucosal proliferation, suggesting that bombesin may play a role in protecting gut integrity.Publication Open Access Propylthiouracil-induced hypothyroidism protects ionizing radiation-induced multiple organ damage in rats(BIOSCIENTIFICA LTD, 2006-05) VELİOĞLU ÖĞÜNÇ, AYLİZ; Sener, G.; Kabasakal, L.; Atasoy, B. M.; Erzik, C.; Velioglu-Ogunc, A.; Cetinel, S.; Contuk, G.; Gedik, N.; Yegen, B. C.The objective of this study was to examine the potential radioprotective properties of propylthiouracil (PTU)-induced hypothyroidism against oxidative organ damage induced by irradiation. Sprague-Dawley rats were pre-treated with saline or PTU (10 mg/kg i.p.) for 15 days, and were then exposed to whole-body irradiation (800 cGy). A group of rats were decapitated at 6 h after exposure to irradiation, while another group was followed for 72 h after irradiation, during which saline or PTU injections were repeated once daily. Lung, liver, kidney and ileum samples were obtained for the determination of malondialdehyde (MDA; an index of lipid peroxidation) and glutathione (GSH, an antioxidant) levels, myeloperoxidase activity (MPO; an index of tissue neutrophil accumulation) and collagen contents, while oxidant-induced DNA fragmentation was evaluated in the ileal tissues. All tissues were also examined microscopically and assayed for the production of reactive oxidants using chemiluminescence (CL). Lactate dehydrogenase (LDH), an indicator of tissue damage, and turnout necrosis factor-alpha (TNF alpha) were assayed in serum samples. Irradiation caused a significant decrease in GSH level, which was accompanied by significant increases in MDA levels, MPO activity, CL levels and collagen content of the tissues studied (P < 0.05-0.001). Similarly, serum TNFa and LDH were elevated in the irradiated rats as compared with the control group. On the other hand, PTU treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. Our results suggested that PTU-induced hypothyroidism reduces oxidative damage in the lung, hepatic, renal and ileal tissues probably due to hypometabolism, which is associated with decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms.Publication Metadata only Inhibitory effects of gastrin releasing peptide on gastric emptying in rats(ELSEVIER SCIENCE BV, 1996) YEGEN, BERRAK; Yegen, BC; Gurbuz, V; Coskun, T; Bozkurt, A; Kurtel, H; Alican, I; Dockray, GJGastrin-releasing peptide (GRP) has a wide range of biological actions, including stimulation of the frequency of antral contractions and delaying gastric emptying. The present study was designed to evaluate the role of GRP in the control of gastric emptying of liquid test meals in the rat. The emptying of methyl cellulose given by gavage to fasted rats, or of saline given via the fistula to conscious gastric fistula rats was not influenced by the GRP antagonists, NC-8-89 (Leu(13)-psi-(CH2NH)-Leu(14)-bombesin) and 2258U89 ((de-NH2)Phe(19),D-Ala(24),D-Pro(26)psi (CH2NH)Phe(27)(-GRP (19-27)), at 2 mg/kg, s.c. However, both antagonists (0.02, 0.2 and 2 mg/kg) reversed the inhibitory effect of HCl on gastric emptying in gastric fistula rats (P < 0.05-0.001). When peptone was administered after a preload, but not otherwise, the inhibition of emptying was also partly reversed by both antagonists at all doses used (P < 0.05-0.001). Interestingly, the delay in the emptying of hyperosmolal saline compared to saline, was enhanced at a dose of 0.2 mg/kg of both antagonists (P < 0.05 and P < 0.01). Food intake did not change significantly with the two lower doses of antagonists, but was decreased by the highest dose of NC 8-89. We conclude that GRP specifically inhibits gastric emptying of acid and peptone solutions in the conscious rat.Publication Metadata only Interactive lecturing for meaningful learning in large groups(TAYLOR & FRANCIS LTD, 2005) YEGEN, BERRAK; Gulpinar, MA; Yegen, BCIn order to enhance the quality of integration of physiological basic concepts with clinical sciences and to facilitate problem solving skills, a 'structured integrated interactive' two-hour block lecture on growth hormone physiology was implemented. A template showing the central regulation of growth hormone release and its peripheral effects was developed as an advanced organizer. Based on this template, new information was presented. Student feedback demonstrated that the lecture, based on the expository teaching model and enhanced by different forms of question and problem solving activities, was successful and interactive. It was also more motivating and was able to keep the attention of the students in relatively higher levels throughout the lecture. Furthermore, students felt that they had made important gains in transferable problem solving skills and this opinion was supported by their performance in clinical cases. These findings reinforced the idea that systematic incorporation of active learning strategies into lectures may minimize many of the weaknesses of traditional lectures.Publication Metadata only The antifibrotic drug halofuginone reduces ischemia/reperfusion-induced oxidative renal damage in rats(ELSEVIER SCI LTD, 2013) YEGEN, BERRAK; Cerit, Kivilcim Karadeniz; Karakoyun, Berna; Yuksel, Meral; Ozkan, Naziye; Cetinel, Sule; Dagli, E. Tolga; Yegen, Berrak C.; Tugtepe, HalilAim: The objective of the present study was to evaluate the protective effects of halofuginone against renal ischemia/reperfusion (I/R) injury. Materials and methods: Male Wistar albino rats were unilaterally nephrectomized and the left renal pedicles were occluded for 45 min to induce ischemia and then reperfused for 6 h (early) or for 72 h (late). The rats were treated intraperitoneally with either halofuginone (100 mu g/kg/day) or saline 30 min prior to ischemia and the dose was repeated in the late reperfusion groups. In the sham groups, rats underwent unilateral nephrectomy and were treated at similar time points. The animals were decapitated at either 6 h or 72 h of reperfusion and trunk blood and kidney samples were obtained. Results: I/R injury increased renal malondialdehyde levels, myeloperoxidase activity and reactive oxygen radical levels, and decreased the renal glutathione content. Halofuginone treatment was found to reduce oxidative I/R injury and improve renal function in the rat kidney, as evidenced by reduced generation of reactive oxygen species, depressed lipid peroxidation and myeloperoxidase activity, and increased glutathione levels. Conclusions: The present findings demonstrate the anti-inflammatory and antioxidant effects of halofuginone in renal I/R injury, supporting its potential use where renal I/R injury is inevitable. (C) 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.Publication Metadata only Melatonin supports alendronate in preserving bone matrix and prevents gastric inflammation in ovariectomized rats(WILEY, 2019) YEGEN, BERRAK; Gurler, Esra Bihter; Cilingir-Kaya, Ozlem Tugce; Eyuboglu, Irem Peker; Ercan, Feriha; Akkiprik, Mustafa; Reiter, Russell J.; Yegen, Berrak C.The anti-catabolic bisphosphonate alendronate is considered as the first-line medical treatment in post-menopausal osteoporosis; but several side effects, including gastric mucosal injury, are associated with its use. The aim was to elucidate whether combined treatment with melatonin plus alendronate would be more advantageous in the maintenance of bone and the prevention of gastric side effects. Under anaesthesia, female Sprague-Dawley rats underwent bilateral ovariectomy (OVX), while control group had sham surgery. Four weeks after the surgery, OVX rats were treated with saline, melatonin (25 mu g/mL/d), alendronate (70 mu g/kg/wk), melatonin + alendronate, melatonin + melatonin receptor antagonist (luzindole, 10 mu g/kg/d) or alendronate + melatonin + luzindole for 8 weeks. Rats were euthanized at the end of 12th week. Runx2 expression, apoptotic cells, and trabecular thickness were evaluated in tibiae, while gastric tissues were analysed for oxidative injury parameters. In all OVX groups, Runx2 expression was depressed. Saline-treated OVX group presented an extreme decrease in calcified area in opposition to melatonin- or alendronate-treated groups, while the bones in alendronate + melatonin-treated group were similar to those of the sham-operated group. Concomitant with the improvements examined histologically in bone tissues, quantitative TUNEL (+) cells were similarly lower in alendronate- or melatonin-treated groups. Oxidative gastric damage was increased in saline- or alendronate-treated groups, which were depressed in the presence of melatonin. Although melatonin and alendronate exerted similar supportive effects on the maintenance of bone mass, melatonin may have a more advantageous impact by protecting against OVX-induced gastric injury, which was aggravated by alendronate use. Highlights Our results demonstrate that alendronate and melatonin had similar supportive effects on the maintenance of bone mass, while melatonin prevented the gastric side effects of alendronate, making this combination an advisable therapeutic approach in the treatment of menopausal osteoporosis.Publication Metadata only Pathways mediating CRF-induced inhibition of gastric emptying in rats(1997) YEGEN, BERRAK; Coşkun, T.; Bozkurt, A.; Alican, I.; Ozkutlu, U.; Kurtel, H.; Yegen, B. C.The corticotrophin-releasing factor (CRF) is shown to be released during stress suggesting that CRF has a physiological role in the mediation of central nervous system (CNS) response to stress, including an inhibitory effect on gastric emptying. In the present study, we have examined the pathways by which intracerebroventricularly (i.c.v.) administered CRF and central CRF activation during stress alter the gastric emptying rate of saline (0.14 M), acid (50 mM), peptone (4.5%) and peptone after preload. The emptying rates of all these test meals were significantly (p < 0.05-0.001) delayed with increasing doses of i.c.v. CRF (0.001, 0.003, 0.01, 0.1, 0.3 and 1 nmol/10 microl), when compared with their i.c.v. saline-treated controls. The 1-nmol dose of CRF inhibited the emptying of acid, peptone and peptone after a preload by 43.8%, 64.1% and 81.1%, respectively. Twenty-minute swim stress delayed gastric emptying rate of saline, acid and peptone solutions significantly (p < 0.001) and the CRF receptor antagonist, alpha-helical CRF (8 nmol/10 microl, i.c.v.), applied before the swim stress, abolished the inhibitory effect of stress on the emptying rate of these solutions. Acute intragastric administration of capsaicin (2 mg/rat) and systemic capsaicin (125 mg kg(-1)) treatment facilitated the gastric emptying rate of acid, peptone and peptone after preload significantly, almost abolishing the inhibitory effect of central CRF (p < 0.001). However, either capsaicin treatment had no effect on stress-induced inhibition of the gastric emptying of none of the solutions, except peptone after a preload. Our findings demonstrate that the gastric inhibitory response induced by swimming as a stress-producing stimulus is mediated by the endogenous release of CRF. They also suggest that CRF exerts its CNS actions on the gastrointestinal tract via vago-vagal, capsaicin-sensitive pathways, probably involving the central cholecystokinin (CCK) mechanisms.Publication Metadata only Oxytocin ameliorates skin damage and oxidant gastric injury in rats with thermal trauma(ELSEVIER SCI LTD, 2008) YEGEN, BERRAK; Iseri, Sevgin Oezlem; Gedik, Ismail Ertugrul; Erzik, Can; Uslu, Bahar; Arbak, Serap; Gedik, Nursal; Yegen, Berrak C.Transient splanchnic vasoconstriction following major burns causes oxidative and/or nitrosative damage in gastrointestinal tissues due to ischemia, which is followed by reperfusion injury. Oxytocin (OT), a hypothalamic nonapeptide, possesses antisecretory and antiulcer effects, facilitates wound healing and is involved in immune and inflammatory processes. To assess the possible protective effect of oxytocin (OT) against burn-induced gastric injury, Sprague-Dawley rats (250-300 g) were randomly divided into three groups as control (n = 8), OT-treated burn (n = 8) and saline-treated burn (n = 8) groups. Under anesthesia, the shaved dorsal skin of rats was exposed to 90 degrees C water for 10 s to induce burn injury covering 30% of total body surface area in a standardized manner. Either oxytocin (5 mu g/kg) or saline was administered subcutaneously immediately after and at 24 h following burn, and the rats were decapitated at 48 h. Serum samples were assayed for TNF-alpha, and stomach was taken for the determination of malondialdehyde (MDA), myeloperoxidase (MPO) activity, DNA fragmentation rate (%) and histopathological examination. MDA and MPO were assayed for products of lipid peroxidation and as an index of tissue neutrophil infiltration, respectively. When compared to control group, burn caused significant increases in gastric MDA and MPO activity and increased microscopic damage scores at 48 h (p < 0.001). Oxytocin treatment reversed the burn-induced elevations in MDA and MPO levels and reduced the gastric damage scores (p < 0.001, p < 0.01), while TNF-alpha levels, which were increased significantly at 48th h after injury (p < 0.001), were abolished with OT treatment (p < 0.001). The results of this study suggest that oxytocin may provide a therapeutic benefit in diminishing burn-induced gastric inflammation by depressing tissue neutrophil infiltration and decreasing the release of inflammatory cytokines, but requires further investigation as a potential therapeutic agent in ameliorating the systemic effects of severe burn. (C) 2007 Elsevier Ltd and ISBI. All rights reserved.Publication Metadata only The neuroprotective and anti-apoptotic effects of melatonin on hemolytic hyperbilirubinemia-induced oxidative brain damage(WILEY, 2016) MEMİŞOĞLU, ASLI; Pazar, Asilay; Kolgazi, Meltem; Memisoglu, Asli; Bahadir, Elif; Sirvanci, Serap; Yaman, Akan; Yegen, Berrak C.; Ozek, ErenMelatonin exerts protection in several inflammatory and neurodegenerative disorders. To investigate the neuroprotective effects of melatonin in an experimental hemolysis-induced hyperbilirubinemia, newborn Sprague-Dawley rats (25-40 g, n = 72) were injected with phenylhydrazine hydrochloride (PHZ; 75 mg/kg) and the injections were repeated at the 24th hour. Rats were treated with saline or melatonin (10 mg/kg) 30 min before the first and second PHZ injections and 24 h after the 2nd PHZ injections. Control rats (n = 24) were injected with saline, but not PHZ. At sixth hours after the last injections of saline or melatonin, all rats were decapitated. Tumor necrosis factor (TNF)-alpha, IL-1 beta, IL-10 and brain-derived neurotrophic factor (BDNF) and S100B levels in the plasma were measured. Brain tissue malondialdehyde (MDA), glutathione (GSH) levels and myeloperoxidase (MPO) activities were measured, and brain tissues were evaluated for apoptosis by TUNEL method. In the saline-treated PHZ group, hemoglobin, hematocrit levels were reduced, and total/direct bilirubin levels were elevated when compared to control group. Increased plasma TNF-alpha, IL-1 beta levels, along with decreased BDNF, S100B and IL-10 values were observed in the saline-treated PHZ group, while these changes were all reversed in the melatonin-treated group. Increased MDA levels and MPO activities in the brain tissues of saline-treated hyperbilirubinemic rats, concomitant with depleted brain GSH stores, were also reversed in the melatonin-treated hyperbilirubinemic rats. Increased TUNEL(+) cells in the hippocampus of saline-treated PHZ group were reduced by melatonin treatment. Melatonin exerts neuroprotective and anti-apoptotic effects on the oxidative neuronal damage of the newborn rats with hemolysis and hyperbilirubinemia.Publication Metadata only Deneysel sepsis modelinde akut kardiyopulmoner ve serebral hasarda nöropeptit W'nin etkisi(2019-12-13) ATICI, ALİ EMRE; PEKER EYÜBOĞLU, İREM; YEGEN, BERRAK; AKKİPRİK, MUSTAFA; ERCAN, FERİHA; ATICI A. E., ARABACI TAMER S., levent h. n., PEKER EYÜBOĞLU İ., ERCAN F., AKKİPRİK M., YEGEN B.Giriş ve Amaç: Ciddi enfeksiyonların neden olduğu sepsis ve beraberinde görülen çoklu organ yetmezliği, yüksek morbidite ve mortalite oranıyla en önemli klinik sendromlardan biridir. Yakın zamanda tanımlanan ve nöroendokrin düzenlemelerde işlev gördüğü gösterilen nöropeptit W (NPW)’nin, deneysel sepsis modeli oluşturularak akciğer, kalp ve beyin dokularında indüklenen oksidatif hasarda olası tedavi edici etkilerini araştırmayı amaçladık. Yöntemler: Ketamin anestezisi altında, Sprague-Dawley erkek sıçanlarda sham-operasyon (n=8) yapıldı veya çekal ligasyon ve perforasyon ile sepsis oluşturuldu (n=64). Post-operatif ciltaltına 3 doz (hemen sonra, 12. ve 24. saatlerde) serum fizyolojik (SF) veya TNF-alfa inhibitörü + antibiyotik (1 mg/kg etanersept + 100 mg/kg seftriakson) veya NPW (0,1; 0,3; 1, 3 ve 10 g/kg) uygulanırken, sham-opere gruba SF enjeksiyonları yapıldı. Yirmibeşinci saatte alınan kan örneklerinde C-reaktif protein (CRP), kortikosteron ve IL-6 düzeyleri ile çıkarılan akciğer, kalp ve beyin dokularında antioksidan glutatyon, lipit peroksidasyonunu gösteren malondialdehit ile nükleer faktör kappa-B (NF- B) mRNA ekspresyon düzeyleri ölçüldü. Hematoksilen-eozin ile histopatolojik değerlendirmeler yapıldı. Verilerin analizinde ANOVA ve Student’ın t-testleri kullanıldı. Bulgular: Etanersept+antibiyotik veya NPW (1-10 g/kg) tedavili sepsis gruplarında IL6, kortikosteron ve CRP düzeyleri SF-tedavili sepsis grubuna göre düşük bulundu (p<0,05-0,001). SFsepsis grubunda beyinde ve akciğerde malondialdehit düzeylerinin arttığı (p<0,01) ve glutatyonun düştüğü (p<0,01) gözlendi. Etanersept+antibiyotik tedavisi veya NPW beyindeki bu değişiklikleri engelledi (p<0,05-0,001). Buna karşın, akciğerde sepsisle artan malondialdehit ve azalan glutatyon düzeylerine antibiyotik+etanersept etkili olmazken, NPW (0,1-0,3 g/kg) akciğerde malondialdehit düzeyini düşürdü (p<0,05-0,01). Kalp dokusunda ölçülen malondialdehit ve glutatyon düzeyleri ile tüm dokularda ölçülen NF- B ekspresyonları açısından gruplar arasında anlamlı fark bulunmadı. SF-tedavili sepsis grubunda gözlenen dejenere nöron sayısında artış, akciğerde şiddetli kanama, alveoler yapıda bozulma ve nötrofil infiltrasyonu ile kardiyomiyositlerdeki konjesyon ve orta derecede hasar gibi değişikliklerin etanersept+antibiyotik ve NPW (10 g/kg) ile hafiflediği ve histolojik yapıların neredeyse normale döndüğü izlendi. Sonuç: Sepsisin ilk 24 saatinde uygulanan NPW, doza bağımlı olarak akciğer ve beyinde oksidatif hasara karşı koruyucu etki göstermektedir.