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Öğe 3 ',4 '-Dihydroxyflavonol attenuates spatial learning and memory impairments in global cerebral ischemia(TAYLOR & FRANCIS LTD, 2017) Öz, Mehmet; Demir, Enver Ahmet; Çalışkan, Merve; Moğulkoç, Rasim; Baltacı, Abdulkerim Kasım; Atalık, Kısmet Esra NurullahoğluObjectives: In the present study, effects of 3', 4'-dihydroxyflavonol (DiOHF) on anxiety-like behavior, and learning and memory were investigated in a model of transient global cerebral ischemia and reperfusion. Methods: The animals were assigned to sham-operated, ischemia, and two DiOHF-treated (10 mg/kg i. p.) groups. DiOHF was administered at 1 hour before and immediately after the ischemia. Male rats were subjected to bilateral common carotid artery occlusion to induce acute cerebral ischemia for 20 minutes, followed by reperfusion for 7 days. The openfield, elevated plus maze (EPM), and Morris water maze tests were used to evaluate the effects of DiOHF treatment on ischemia-induced locomotor activity, anxiety-like behavior, and spatial and recognition memory impairments, respectively. Results: In the open field test, locomotor activity in the ischemic rats was not altered 6 days after the ischemia, nor was anxiety-like behavior, which was evaluated with the EPM (P > 0.05). In the water-maze test, cerebral ischemia significantly decreased the exploration time in the target quadrant, and the platform crossing counts were lower (P < 0.05) in the probe trial test; this memory impairment was significantly improved by DiOHF applied 1 hour before and immediately after ischemia (P < 0.05). Discussion: All together, these findings suggest that DiOHF reverses spatial learning and memory deficits resulting from transient global ischemia but has no significant effect on anxiety-like behavior.Öğe Antidepressant-like effects of quercetin in diabetic rats are independent of hypothalamic-pituitary-adrenal axis(CAMBRIDGE UNIV PRESS, 2016) Demir, Enver Ahmet; Gergerlioglu, Hasan Serdar; Oz, MehmetObjective Quercetin, one of the most potent flavonol in the family of flavonoids, has been shown to have benefits against diabetes and its complications. In the present study, we investigated effects of quercetin on depression-like behaviours and hypothalamic-pituitary-adrenal (HPA) axis in diabetic rats. Methods Experimental diabetes was induced by using streptozotocin, and either 50 or 100 mg/kg quercetin was intraperitoneally administered for 21 days. Following the last treatment, animals were subjected to the forced swim test, and subsequently, the blood was obtained by cardiac puncture to measure plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels. Results A significant increase of the total immobile time, accompanied by a decrease in the immobility latency, which suggests a depressive status, was observed in diabetic animals that was reversed by the treatment of 50 mg/kg quercetin. However, the higher dose of quercetin (100 mg/kg) was ineffective in alleviating depression-like behaviours. The plasma concentrations of ACTH, and total- and free-CORT were not affected by both doses of quercetin. Conclusion Therefore, we concluded that the antidepressant-like effects of quercetin in diabetes are independent of the HPA axis.Öğe Co-administration of cisplatin and curcumin does not alter mood-associated behaviors(COMENIUS UNIV, 2016) Demir, Enver Ahmet; Öz, Mehmet; Alp, Muhammed İkbal; Gergerlioğlu, Hasan Serdar; Atalık, Kısmet Esra Nurullahoğlu; Yerlikaya, Fatma HümeyraOBJECTIVES: Cisplatin (cis-diamminedichloroplatinum (II)) is a widely-used platinum-based chemotherapeutic agent which has dose-limiting side-effects. Also, the drug resistance is another instance that decreases treatment success in cisplatin chemotherapy. The growing body of evidence suggests that curcumin, a polyphenolic compound extracted from the spice turmeric, may exert synergistic effects and sensitize malign cells to cisplatin, while alleviating cytotoxicity-related side-effects. The present study was aimed to investigate mood-associated interactions between cisplatin and curcumin. MATERIALS AND METHODS: Thirty-four adult male Wistar albino rats were randomly assigned to four groups as control, curcumin (300 mg/kg/day, p.o. for 5 weeks), cisplatin (5 mg/kg/week, i.p. for 5 weeks), and curcumin plus cisplatin (same doses as above). The open field, elevated plus maze, and forced swim tests were engaged to evaluate mood-associated behaviors. RESULTS: We demonstrated that depression- and anxiety-like behaviors were not altered by the administration of curcumin along with the chronic cisplatin treatment. CONCLUSION: According to the results of the present study, we concluded that curcumin might be regarded as a safe adjuvant in cisplatin chemotherapy in terms of the mood-associated behaviors (Fig. 4, Ref 41).Öğe The Effect of Alpha Lipoic Acid on the Hypothalamic-pituitary-adrenal Axis and Cholinergic System in an Experimental Alzheimer's Model(WILEY-BLACKWELL, 2016) Oz, Mehmet; Demir, Enver Ahmet; Gergerlioglu, Hasan Serdar[Abstract not Available]Öğe Effect of different doses of Quercetin supplementation on element levels of brain tissue in diabetic rats(WILEY-BLACKWELL, 2014) Demir, Enver Ahmet; Yazgan, Betül; Öz, Mehmet; Alp, Muhammed İkbal; Gergerlioğlu, Hasan Serdar; Moğulkoç, Rasim; Baltacı, Abdulkerim Kasım[Abstract not Available]Öğe Effects of Cisplatin and Curcumin on the Hypothalamic-Pituitary-Adrenal Axis(WILEY-BLACKWELL, 2015) Öz, Mehmet; Demir, Enver Ahmet; Gergerlioğlu, Hasan Serdar; Atalık, Kısmet Esra Nurullahoğlu; Yerlikaya, Fatma Hümeyra[Abstract not Available]Öğe Effects of the Environmental Enrichment on Learning and Memory in High-Fat Diet-Fed Rats(WILEY-BLACKWELL, 2015) Öz, Mehmet; Demir, Enver Ahmet; Gergerlioğlu, Hasan Serdar; Atalık, Kısmet Esra Nurullahoğlu; Yerlikaya, Fatma Hümeyra[Abstract not Available]Öğe Environmental enrichment reverses cognitive impairments provoked by Western diet in rats: Role of corticosteroid receptors(PERGAMON-ELSEVIER SCIENCE LTD, 2016) Gergerlioğlu, Hasan Serdar; Öz, Mehmet; Demir, Enver Ahmet; Atalık, Kısmet Esra Nurullahoğlu; Yerlikaya, Fatma HümeyraAims: Previous studies demonstrated that the Western diet (WD), which is rich in saturated fat (HFD) and refined sugar (HSU), is related to the impairments of hippocampus-dependent learning and memory and forebrain synaptic plasticity in rodents. The environmental enrichment (EE) has been shown to enhance learning and memory in theHFD-induced cognitive deficits, but the exact mechanismis still not clearly understood. Therefore, the present study aimed to clarify the effects of the EE on spatial memory in WD-fed rats, and to analyze the potential role of corticosteroid receptors in the EE conditioning. Main methods: MaleWistar albino rats were housed in either an enriched or standard environment and fed with the HFD (35% of energy as fat), HSU (100% of carbohydrate as sucrose) or standard rat chowfor 4 weeks. Weused the Morris' water maze test (MWM) to assess the learning and memory performance, and measured plasma levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH), as well as glucocorticoid (GR) and mineralocorticoid receptor (MR) levels in the hippocampus. Key findings: The results showed that HFD-fed rats displayed poorer learning and memory performance evaluated with MWM than controls. The EE reversed the cognitive deficits caused by the HFD. In addition, the EE resulted in an increase of GR and MR levels without affecting plasma CORT and ACTH concentrations. Significance: Based on these findings, it could be suggested that the EE plays an important role in amelioration of the HFD-induced cognitive impairments, but this intervention is independent of the hypothalamic-pituitaryadrenal axis and hippocampal corticosteroid receptor levels. (C) 2016 Elsevier Inc. All rights reserved.Öğe Hipotalamik-hipofizer-adrenal Aks Üzerine Sisplatin ve Kurkuminin Etkileri(Selçuk Üniversitesi, 2017 Mart) Öz, Mehmet; Demir, Enver Ahmet; Gergerlioğlu, Hasan Serdar; Atalık, Kısmet Esra Nurullahoğlu; Yerlikaya, Fatma HümeyraAmaç: Son yıllarda zerdeçaldaki aktif polifenol olan kurkumininsisplatin içeren kemoterapi rejimlerinde sinerjistik bir role sahip olduğunu gösteren bilgiler artmaktadır. Kurkuminin güvenli bir adjuvan olduğunu göstermek için söz konusu ajanların sistemik etkileşimlerinin araştırılması gerektiğinden bu polifenolünsisplatin uygulanan sıçanlarda hipotalamik-hipofizer-adrenal (HPA) aksa etkilerinin incelemesi amaçlandı. Gereç ve Yöntem: Toplamda 34 erkek Wistar sıçan kontrol (n=7), sisplatin (n=10), kurkumin(n=7) ve sisplatin + kurkumin (n=10) olmak üzere dört gruba ayrıldı. Sisplatin ve kurkumin gruplarındaki sıçanlara 5 hafta süresince (sırasıyla) 5 mg/kg/hafta, i.p. sisplatin ve 300 mg/ kg/gün, p.o. kurkumin uygulandı. Sisplatin + kurkumin grubu aynı dozlarda hem sisplatin hem kurkumin aldı. Kontrol grubuna yalnızca taşıyıcı (fizyolojik salin ve mısır yağı) verildi. Hayvanlar adrenokortikotropik hormon (ACTH) ve kortikosteron (CORT) ölçümleri için kan elde etmek maksadıyla eksanguine edildi. Beyin çıkarıldı ve hipokampal dokuda mineralokortikoid (MR) ve glukokortikoid (GR) reseptörleri belirlendi. Analizler ELISA yöntemiyle gerçekleştirildi. Bulgular: Sisplatin ve kurkumin tedavilerinin araştırılan parametreleri bozmadığını bulduk (p>0.05). Ayrıca, kurkumin ve sisplatinin birlikte uygulanmasının kontrollere kıyasla ACTH ve CORT’un plazma konsantrasyonları ile hipokampal MR ve GR seviyelerini değiştirmediğini gözlendi (p>0.05). Sonuç: Sonuçlarımıza göre tek başına veya kombine halde sisplatin ve kurkumin tedavisi HPA aksını etkilememektedir.Öğe Impact of enriched environment on production of tau, amyloid precursor protein and, amyloid-beta peptide in high-fat and high-sucrose-fed rats(CAMBRIDGE UNIV PRESS, 2017) Selvi, Yavuz; Gergerlioğlu, Hasan Serdar; Akbaba, Nursel; Öz, Mehmet; Kandeğer, Ali; Demir, Enver Ahmet; Yerlikaya, Fatma HümeyraObjective: The Western-type diet is associated with an elevated risk of Alzheimer's disease and other milder forms of cognitive impairment. The aim of the present study was to investigate the effects of the environmental enrichment on amyloid and tau pathology in high-fat and high-sucrose-fed rats. Methods: In total, 40 adult male rats were categorised into two main groups according to their housing conditions: enriched environment (EE, n = 16) and standard housing condition (n = 24). The groups were further divided into five subgroups that received standard diet, high-fat diet, and high-sucrose diet. We performed the analysis of amyloid beta-peptide (A beta) (1-40), A beta(1-42), amyloid precursor protein (APP), and tau levels in the hippocampus of rats that were maintained under standard housing conditions or exposed to an EE. Results: The EE decreased the A beta(1-40), A beta(1-42), APP, and tau levels in high-fat and high-sucrose-fed rats. Conclusion: This observation shows that EE may rescue diet-induced amyloid and tau pathology.Öğe Quercetin and caffeic acid phenethyl ester (CAPE) attenuate acute exercise-induced oxidative stress(MATTIOLI 1885, 2015) Gergerlioglu, Hasan Serdar; Gokbel, Hakki; Okudan, Nilsel; Gergerlioglu, Nursadan; Demir, Enver AhmetFlavonoids are naturally occurring antioxidant molecules that are abundantly existing in the human diet. We investigated effects of quercetin and caffeic acid phenethyl ester to redox balance in acute treadmill exercise. Malondialdehyde, superoxide dismutase activity, xanthine oxidase activity and total nitrite in blood, skeletal muscle and liver were analyzed in 58 male Sprague-Dawley rats that were exposed to a single bout of exercise. We found that exercise provoked the increment of analyzed parameters except for total nitrite which indicates nitric oxide. Quercetin and caffeic acid phenethyl ester decreased malondialdehyde levels in skeletal muscle and liver. However, they were ineffectual in preventing lipid peroxidation in blood probably due to limited repair and biosynthesis capability of erythrocytes. Since quercetin and CAPE successfully weakened oxidative stress in liver and skeletal muscle, they may be seen as promising in preventing acute exercise-induced oxidative injury.Öğe Streptozotosin ile indüklenmiş diyabetik rat modelinde kuersetinin HPA aksı ve depresyona etkisi(Selçuk Üniversitesi Sağlık Bilimleri Enstitüsü, 2014) Demir, Enver Ahmet; Gergerlioğlu, Hasan SerdarFlavonoid ailesinin en güçlü flavonollerinden biri olan kuersetinin sağlık açısından çeşitli faydaları gösterilmiştir. Depresyon fizyopatogenezinde söz edilen oksidatif stres, enflamasyon ve hipotalamik-hipofizer-adrenal aks disregülasyonu diyabetik komplikasyonlarla da ilişkilidir. Bu çalışmada yan etkiler ve tedavi uyumsuzluğu nedeniyle geleneksel antidepresan ilaç tedavilerinin sınırlı fayda sunduğu diyabette kuersetinin antidepresan benzeri karakteri ve hipotalamik-hipofizer-adrenal aks üzerine etkileri araştırılmıştır. Bu amaçla diyabetik ve non-diyabetik iki ana grupta; kontrol, 50 mg/kg ve 100 mg/kg i.p. kuersetin uygulanan üçer alt grup olacak şekilde toplam altı grupta 45 erişkin erkek sıçan kullanılmıştır. Tek doz streptozotosin (60 mg/kg) uygulamasından 72 saat sonra kan glukozu tayiniyle diyabet doğrulamasını takiben 21 gün süreyle kuersetin uygulamaları gerçekleştirilmiş ve haftalık ağırlık takibi yapılmıştır. 14. ve 21. günlerde kan glukozu ölçülmüştür. Porsolt testi amacıyla son uygulamadan bir gün önce 15 dakika süreyle aklimatizasyon ve son uygulamadan sonra 5 dakika süreyle test seansları yürütülmüştür. Test sonrasında elde edilen plazmadan adrenokortikotropik hormon, total kortikosteron, serbest kortikosteron, nitrik oksit (total nitrit) ve malondialdehit seviyeleri ölçülmüştür. Diyabetin hayvanlarda kilo kaybına yol açtığı, 100 mg/kg kuersetin uygulamasıyla bu kaybın azaldığı görülmüştür. İki farklı dozdaki kuersetinin diyabete sekonder gelişen hiperglisemi üzerine etkilerinin bulunmadığı belirlenmiştir. Hem diyabetik hem non-diyabetik hayvanlarda 50 mg/kg kuersetin uygulamasının Porsolt testinde total immobil süreyi azaltırken immobilite latensini uzattığı; ancak 100 mg/kg kuersetin uygulamasının diyabetik hayvanlarda total immobil süre ve immobilite latensi üzerine etkisinin bulunmadığı görülmüştür. Kuersetinin kullanılan iki dozunun da diyabetik ve non-diyabetik hayvanlarda adrenokortikotropik hormon, total kortikosteron ve serbest kortikosteron seviyelerini etkilemediği belirlenmiştir. Diyabet veya kuersetin uygulamaları nitrik oksit düzeyini değiştirmediği halde malondialdehit seviyeleri diyabetle birlikte artış göstermiş ve kuersetin uygulamasıyla non-diyabetik hayvanlardaki seviyesine inmiştir. Çalışmamızın sonuçları değerlendirildiğinde 50 mg/kg kuersetin uygulamasının diyabetik deneklerde antidepresan benzeri aktivite sergilediği; ancak söz konusu etkinin 100 mg/kg kuersetin uygulanmasıyla oluşmadığı anlaşılmıştır. Diyabetin hipotalamik-hipofizer-adrenal aksı bozmaması, kullanılan modelin süresiyle ilişkilendirilmişken antidepresan etkinlik gösteren ve göstermeyen kuersetin dozlarının aksı değiştirmemesi nedeniyle kuersetinin diyabetik hayvanlarda görülen antidepresan benzeri etkinliğinin hipotalamik-hipofizer-adrenal akstan bağımsız olduğu sonucuna varılmıştır.