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Öğe Glutamat İle İndüklenen Nöron Hasarında Floretin ve Florizinin Etkileri: İn Vitro Çalışma(2019) Binnetoğlu, Damla; Yayla, Muhammed; Yüksel, Tuğba NurcanAmaç:Çalışmamızda eksitatör bir nörotransmitter olan glutamata bağlı nörotoksisitenin önlenmesi amacıyla güçlü antioksidan, antiinflamatuar ve antiapoptotik olan floretin ve florizinin etkilerini araştırmayı amaçladık.Materyal ve Metot:Çalışmamızda yeni doğan sıçan korteksi kullanıldı. 10-5 M ve 2x10-5 M konsantrasyonlarında floretin ile 10-5 M ve 2x10-5 M konsantrasyonlarında florizin ayrı ayrı uygulandıktan 2 saat sonra 3x10-3 M ve 6x10-3 M konsantrasyonlarında glutamat uygulaması gerçekleştirildi. Glutamat uygulamasından 6 saat sonra hücrelerden mRNA izolasyonu yapıldı. 24 saat sonra ise metiltiazol difenil tetrazolium (MTT) testi, total oksidan ve antioksidan kapasite ölçümleri gerçekleştirildi.Bulgular:Çalışmamızda glutamat artan dozlarda hücre canlılığını azaltırken floretin ve florizin uygulaması yüksek dozda en iyi nöroprotektif etkiyi ortaya koydu. Toksisiteye bağlı artan total oksidan düzey floretin ve florizin tarafından anlamlı derecede düzeltildi. Toksisite oluşturulan grupta azalan antioksidan kapasite floretin ve florizin uygulaması ile düzelme gösterdi. Floretin ve florizin tek başlarına uygulandığında hücre canlılığını anlamlı derecede etkilemezken, antioksidan kapasiteyi artırdı, oksidan düzeyi ise azalttı. Glutamat uygulaması sonrası artan tümör nekroz faktör-alfa (TNF-?) mRNA ekspresyonu, floretin ve florizin uygulaması ile anlamlı derecede azaldı. Glutamat uygulamasına bağlı artan kaspaz 9 ve kaspaz 3 mRNA ekspresyonu ise floretin ve florizin uygulaması ile anlamlı derecede düzelmegösterdi.Sonuç:Bu bulgular, güçlü antioksidan, antiinflamatuar ve antiapoptotik olan floretin ve florizinin glutamata bağlı gelişen nörotoksisitede koruyucu olabileceğini ve glutamatın neden olduğu nörolojik bozuklukların önlenmesi için terapötik ajanlar olarak kullanılabileceğini gösterir.Öğe INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS(2023) Yüksel, Tuğba Nurcan; Yayla, Muhammed; Köse, Duygu; Ugan, Rüstem Anıl; Tokay, Erdem; Kılıcle, Pınar Aksu; Çadırcı, ElifPomegranate peel contains bioactive ingredients such as flavonoids, ellagitannins, phenolics and proanthocyanidin compounds with high antioxidant activity. Pomegranate peel has antiapoptotic, antioxidant and anti-inflammatory effects due to its high punicalagin content. We aimed to determine the effect of pomegranate peel extract (PPE) on lipopolysaccharide (LPS)-induced uveitis. Sixty rats were seperated randomly into twelve groups (n = 5). The healthy group received intraperitoneal normal saline, the uveitis group received 200 ?g/kg LPS, the dexamethasone (DEX) group received 200 ?g/kg LPS plus 1 mg/kg DEX, the PPE100, PPE300 and PPE500 groups received 200 ?g/kg LPS plus 100, 300 and 500 mg/kg PPE, respectively. The eye tissues were collected at 3rd and 24th hour. and investigated molecularly (Relative quantification of gene expression), biochemically (Superoxide dismutase activity, Glutathione and Malondialdehyde levels) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Tumor Necrosis Factor-?, vascular endothelial growth factor, and Caspase-3 levels markedly decreased in a dose-dependent manner in the uveitic rats following PPE administration. PPE administration significantly ameliorated uveitic disorders in oxidative stress factors including Glutathione, Superoxide dismutase and Malondialdehyde, with its effects raising in a dose-dependent manner. PPE eliminated histopathological changes in eye tissues due to uveitis. PPE can be a promising agent by contributing to alternative preventive treatment methods for uveitis with its anti-inflammatory, antioxidative, antiapoptotic and antiangiogenic effects.Öğe INVESTIGATION OF THE PROTECTIVE EFFECTS OF POMEGRANATE (Punica granatum L.) PEEL EXTRACT ON LIPOPOLYSACCHARIDE-INDUCED UVEITIS IN RATS(Trakya Univ Balkan Yerlesesi Enstituler Binasi, 2023) Yuksel, Tugba Nurcan; Yayla, Muhammed; Kose, Duygu; Ugan, Rustem Anil; Toktay, Erdem; Aksu Kilicle, Pinar; Cadirci, ElifPomegranate peel contains bioactive ingredients such as flavonoids, ellagitannins, phenolics and proanthocyanidin compounds with high antioxidant activity. Pomegranate peel has antiapoptotic, antioxidant and anti-inflammatory effects due to its high punicalagin content. We aimed to determine the effect of pomegranate peel extract (PPE) on lipopolysaccharide (LPS)-induced uveitis. Sixty rats were seperated randomly into twelve groups (n = 5). The healthy group received intraperitoneal normal saline, the uveitis group received 200 mu g/kg LPS, the dexamethasone (DEX) group received 200 mu g/kg LPS plus 1 mg/kg DEX, the PPE100, PPE300 and PPE500 groups received 200 mu g/kg LPS plus 100, 300 and 500 mg/kg PPE, respectively. The eye tissues were collected at 3rd and 24th hour. and investigated molecularly (Relative quantification of gene expression), biochemically (Superoxide dismutase activity, Glutathione and Malondialdehyde levels) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Tumor Necrosis Factor-alpha, vascular endothelial growth factor, and Caspase-3 levels markedly decreased in a dose-dependent manner in the uveitic rats following PPE administration. PPE administration significantly ameliorated uveitic disorders in oxidative stress factors including Glutathione, Superoxide dismutase and Malondialdehyde, with its effects raising in a dose-dependent manner. PPE eliminated histopathological changes in eye tissues due to uveitis. PPE can be a promising agent by contributing to alternative preventive treatment methods for uveitis with its anti-inflammatory, antioxidative, antiapoptotic and antiangiogenic effects.Öğe Protective effect of 5-HT7 receptor activation against glutamate-induced neurotoxicity in human neuroblastoma SH-SY5Y cells via antioxidative and antiapoptotic pathways(Pergamon-Elsevier Science Ltd, 2019) Yüksel, Tuğba Nurcan; Yayla, Muhammed; Halıcı, Zekai; Çadırcı, Elif; Polat, Beyzagül; Köse, DuyguSerotonin exerts anti-inflammatory, antioxidant and antiapoptotic effects through 5-HT7 receptors. The present study determined the role of 5-HT7 receptors in glutamate-induced neurotoxicity by using human SH-SY5Y neuroblastoma cells. The cells were pretreated with different concentrations of 5-HT7 receptor agonist LP44 and antagonist SB269970 for 60 min, followed by treatment with glutamate. Cell proliferation was measured using xCELLigence system. Treatment with all the concentrations of LP44 significantly protected the cells from the toxic effects of glutamate after 24, 48 and 72 h. Although 5-HT7 receptor expression was significantly upregulated in glutamate-treated cells, it was downregulated in LP44-pretreated cells. Furthermore, LP44 treatment significantly decreased malondialdehyde levels and increased superoxide dismutase activities and glutathione levels. Moreover, LP44 treatment significantly decreased tumor necrosis factor alpha (TNF-a) levels and inhibited caspase 3 and caspase 9 mRNA expression. In contrast, SB269970 treatment exerted an insignificant effect on oxidative stress, inflammation and apoptosis. These findings suggest that exogenous stimulation of the 54-1T7 receptors may be protective in glutamate-induced neurotoxicity and that 5-HT7 receptor agonists can be used as therapeutic agents for preventing glutamate-induced neurological disorders.Öğe Protective effects of melatonin receptor agonists on endotoxin- induced uveitis in rats(Mashhad Univ Med Sciences, 2023) Yüksel, Tuğba Nurcan; Yayla, Muhammed; Köşe, Duygu; Halıcı, Zekai; Bozkurt, Erdinç; Toktay, ErdemObjective(s): Melatonin has an important role in regulating a variety of physiological functions of the body. We investigated the protective effects of Agomelatine (AGO) and Ramelteon (RAME) on Endotoxin-Induced Uveitis (EIU) in rats. Materials and Methods: 70 rats were randomly divided into fourteen groups. Healthy group normal saline, (IP), Uveitis group (200 pg/kg lipopolysaccharide (LPS), SC), DEX group (200 pg/kg LPS plus 1 mg/kg dexamethasone, IP), AGO20 group received 200 pg/kg LPS plus 20 mg/kg AGO, AGO40 group received 200 pg/kg LPS plus 40 mg/kg AGO, RAME2 group received 200 pg/kg LPS plus 2 mg/kg RAME, and group RAME4 received 200 pg/kg LPS plus 4 mg/kg RAME. Each group had two subgroups: the 3rd and 24th hour. The eye tissues were collected and investigated biomicroscopically (clinical manifestations and scoring, molecularly(qRT-PCR analyses of Tumor Necrosis Factor-alpha (TNF-alpha), vascular endothelial growth factor(VEGF), and Caspase 3 and Caspase 9 mRNA expression), biochemically (Superoxide dismutase activity, Glutathione, and Malondialdehyde levels) and histopathologically (staining with Harris Hematoxylin and Eosin Y). Results: Melatonin receptor agonist treatment reduced the clinical score count of ocular inflammation in the uveitic rats. TNF-alpha, VEGF, Caspase 9, and Caspase 3 levels markedly decreased in the uveitic rats. Melatonin receptor agonists significantly ameliorated fixed changes in GSH, SOD, and MDA levels. Melatonin receptor agonists also ameliorated histopathological injury in eye tissues associated with uveitis. Conclusion: Melatonin receptor agonists ameliorated the inflammatory response in EIU. These findings suggest that melatonin receptor agonists may represent a potential novel therapeutic drug for uveitis treatment.Öğe THE EFFECT OF QUERCETIN AND QUERCETIN-3-D-XYLOSIDE ON BREAST CANCER PROLIFERATION AND MIGRATION(Dokuz Eylul Univ Inst Health Sciences, 2022) Yüksel, Tuğba Nurcan; Bozgeyik, Esra; Yayla, MuhammedBackground and Purpose: The aim of this study is to investigate the migration, wound healing, colony formation, and cytotoxic effects of Quercetin-3-D-xyloside (reynoutrin), a quercetin derivative, in breast cancer cells Methods: In the present study, CRL-4010, MCF7 and MDA-MB-231 cells were used to evaluate the cytotoxic, antiproliferative and migration effects of reynoutrin on breast cancer. The IC50 concentration (400 mu g/ml) of reynoutrin, quercetin and cisplatin in the cells was determined. For cytotoxicity assessments, varying concentrations of quercetin, reynoutrin and cisplatin were applied and incubated 24h and 48h. In addition, to examine effects of reynoutrin on migration, cells were seeded in 6-well plates and incubated for 24 hours. For the colony formation assay cells were seeded to 12-well plates at a concentration of 1000 cells/well and incubated overnight. Results: These results indicated that reynoutrin markedly inhibit the cell viability in breast cancer. Conclusion: We have demonstrated for the first time with the present study that reynoutrin suppressed the progression of breast cancer cell proliferation induction and may provide a potential therapeutic target for breast cancer treatment. However, these results should be further confirmed by future more comprehensive studies.
