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Öğe The antioxidant role of agomelatine and gallic acid on oxidative stress in STZ induced type I diabetic rat testes(Elsevier France-Editions Scientifiques Medicales Elsevier, 2017) Yigitturk, Gurkan; Acara, Ahmet Cagdas; Erbas, Oytun; Oltulu, Fatih; Yavasoglu, Nefise Ulku Karabay; Uysal, Aysegul; Yavasoglu, AltugDiabetes is a multisystem disorder and its effects are observed on the reproductive system. One of the main causes of testicular tissue damage is diabetes-induced overproduction of reactive oxygen species and glycated end products. The main objectives of this study were to investigate the possible effects of agomelatine (AG) and gallic acid (GA) in suppressing oxidative stress in Type I diabetes induced testicular damage. A total of 28 adult male rats were included in the study. Diabetes was induced by intraperitoneal injection of streptozocin (STZ, 55 mg/kg) to 21 rats, which were then randomly assigned to 3 groups; 1 mL saline solution was given to the diabetes + saline group by oral gavage, 20 mg/kg/day oral AG was given to the diabetes + AG group, and 20 mg/kg/day oral GA was given to the diabetes + GA group for 4 weeks. Tumor necrosis factor alpha (TNF alpha), nitric oxide synthase 2 (NOS2), fibronectin and vascular endothelial growth factor (VEGF) were used for the investigation of inflammation, fibrosis and vascular structures. The terminal-deoxynucleoitidyl-transferase mediated nick end-labeling assay (TUNEL) was used to detect apoptosis. Testicular tissue total antioxidant capacity values were tested by biochemical analysis. AG treatment showed an improvement on biochemical parameters and histopathological appearance on the rat testes. GA showed dose-related regenerative effects on biochemical parameters. Histologically, a minimal healing effect was determined on the testes damage. In conclusion, it was observed that AG is a potentially beneficial agent for reducing testicular damage by decreasing oxidative stress level. However, GA was seen to have a poor therapeutic effect. (C) 2016 Elsevier Masson SAS. All rights reserved.Öğe Apoptosis-inducing activities of Halopteris scoparia L. Sauvageau (Brown algae) on cancer cells and its biosafety and antioxidant properties(Springer, 2019) Guner, Adem; Nalbantsoy, Ayse; Sukatar, Atakan; Yavasoglu, Nefise Ulku KarabayThe aim of this study was to reveal the biological activities and in vivo toxicity profiles of n-hexane, chloroform and methanol extracts of brown algae Halopteris scoparia L. Sauvageau. In this study, extracts were tested for their phytochemical contents and antioxidant activities. The cytotoxic activities of the extracts against cervical adenocarcinoma (HeLa), colon colorectal adenocarcinoma (CaCo-2) and breast adenocarcinoma (MCF7) cells were assessed by MTT assay and total RNAs derived from cell lines to analyze gene expression were analyzed by Real Time Ready Human Apoptosis Panel 96. Also, in vivo toxicity and irritation effects of extracts were evaluated by LD50 acute toxicity test and Hen's egg test chorioallantoic membrane (HET-CAM) assay, respectively. Our results showed that the phenolic and flavonoid contents were determined only in methanol extract (33.20 +/- 1.41mg GAE/g and 1.26 +/- 0.95mg QE/g). Also, n-hexane has a broader spectrum of content than methanol and chloroform extracts. Furthermore, n-hexane extract in DPPH and methanol extract in ABTS(+) exhibited the best antioxidant activity. In addition, MTT results revealed that each three extracts cause a significant reduction in cell viability, especially in HeLa cells. When the apoptotic gene expressions were examined after treatment of extracts, the expression of many pro-apoptotic genes in both caspase-independent and caspase-dependent intrinsic and extrinsic pathways increased. These findings suggest that, considering that it had not led to irritation and toxicity in vivo, edible H. scoparia is a natural antioxidant and its apoptotic/cytotoxic activities can potentially be used against human cancers.Öğe Apoptosis-inducing activity of safflower (Carthamus tinctorius L.) seed oil in lung, colorectal and cervix cancer cells(Springer, 2020) Guner, Adem; Kizilsahin, Sadi; Nalbantsoy, Ayse; Yavasoglu, Nefise Ulku KarabayCarthamus tinctorius L. (Safflower) has been often preferred because of rich fatty acid, flavonoid, alkaloid, and polysaccharide contents in its different parts in medicine and industrial area. Although its antioxidant, antienflamatuar, and antitumor properties have been proven in many studies, the mechanism underlying the anticancer activity is still more unclear. This study was first conducted to elucidate the apoptotic gene expression changes in human colorectal (CaCo-2), lung (A549), and cervix cancer (HeLa) cells after exposure to safflower seed oil (SFO). Cytotoxic activity of cancer cells was evaluated by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl2H-tetrazoliumbromide) assay and then, total RNA derived from cell lines to analyze the gene expression profile on Real-Time Ready Human Apoptosis Panel 96 was used. MTT results showed that SFO greatly inhibited A549, CaCo-2 and HeLa cell proliferation, with a value of IC50 of 1.26, 3.92 and 13.12 mu g/ml, respectively. According to the cDNA microarray analysis, 56 genes were interpreted in connection with extrinsic, intrinsic, PI3K/AKT, JAK/STAT, and NF kappa B pathways. SFO treatments triggered apoptosis through the caspase-dependently pathway along with upregulated the expressions of many pro-apoptotic genes in the extrinsic and intrinsic pathway in HeLa cells. However, in A549 and CaCo-2 cells, SFO treatments were inhibited cell survival mechanism through frequently caspase-independent genes following downregulated the expression of anti-apoptotic genes. It is noteworthy that although cancer cells have different sensitivity, SFO induced apoptosis through different pathways. Taken together, SFO, as a natural resource, has the potential to be used as a promising agent against cancer, especially in gene therapy level.Öğe Fluvastatin alleviates doxorubicin-induced cardiac and renal toxicity in rats via regulation of oxidative stress, inflammation, and apoptosis associated genes expressions(Taylor & Francis Ltd, 2022) Kuscu, Gokce Ceren; Gurel, Cevik; Buhur, Aylin; Yavasoglu, Nefise Ulku Karabay; Kose, Timur; Yavasoglu, Altug; Oltulu, FatihDoxorubicin (DOXO) is a cytostatic agent used in the chemotherapy protocol of several cancers for more than 40 years, but usage of this drug in cancer treatment has been limited due to severe renal and cardiac tissue toxicities that may result in death in patients. Fluvastatin (FV) is a fully synthetic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor used as a cholesterol-lowering agent in patients with hypercholesterolemia. Previous studies revealed that FV also exhibits antioxidant, anti-inflammatory, and antitumor activity. Additionally, our previous study indicated that FV exerts a prophylactic effect on DOXO-induced testicular toxicity by preventing lipid peroxidation, supporting the antioxidant system, and regulating the blood-testis barrier-associated genes expression. Herein, we purposed to evaluate the possible therapeutic and the protective effects of FV on the DOXO-induced cardiac and renal toxicitiy model by histochemical, immunohistochemical, biochemical, and real-time polymerase chain reaction (real-time PCR) analyses. Results point out protective use of FV exerts a beneficial effect by repressing lipid peroxidation and by regulating the inducible nitric oxide synthase (iNOS), nitric oxide synthase endothelial (eNOS), nuclear factor kappa-B (NF-kappa B), and Caspase-3 (Casp3) protein and mRNA expressions, which play an important role in mediating DOXO-induced renal and cardiac toxicity mechanisms. In conclusion, FV may be a candidate agent for the prevention of renal and cardiac toxicities in cancer patients receiving DOXO chemotherapy.Öğe Medium modification with bone morphogenetic protein 2 addition for odontogenic differentiation(Sociedade Brasileira De Pesquisa Odontologica, 2016) Atalayin, Cigdem; Tezel, Huseyin; Dagci, Taner; Yavasoglu, Nefise Ulku Karabay; Oktem, GulperiThe aim of this study was to evaluate whether medium modification improves the odontogenic differentiation of human dental pulp stem cells (DPSC) in vitro and in vivo. DPSC isolated from human impacted third molar teeth were analysed for clusters of differentiation with flow cytometry. Odontogenic differentiation was stimulated by medium modification with the addition of bone morphogenetic protein 2 (BMP2). The expression of dentin sialophosphoprotein, dentin matrix protein 1, enamelysin/matrix metalloproteinase 20 and the phosphate-regulating gene with homologies to endopeptidases on the X chromosome of the cells were analysed with RT-PCR at 7, 14 and 21 days. Then, DPSC were transplanted on the back of immunocompromised mice via a hydroxyapatite tricalcium phosphate scaffold, and the structure of the formed tissue was investigated. The cells were identified as mesenchymal stem cells with a 98.3% CD73 and CD90 double-positive cell rate. The increase in mineralization capacity and expression of human enamel-dentin specific transcripts proportional to the culture period were determined after differentiation. Six weeks after transplantation, an osteo-dentin matrix was formed in the group in which odontogenic differentiation was stimulated, and the odontogenic characteristics of the matrix were confirmed by histological examination and RT-PCR analysis. Odontogenic differentiation of the isolated and characterized human DPSC was improved with medium modification by the addition of BMP2 in vitro and in vivo. The defined medium and applied technique have a potential use for forming reparative dentin in the future, but the effects of the method should be investigated in long-term studies.Öğe Preparation of a Tc-99m-labeled graft polymer and its in vitro and in vivo evaluation(Springer, 2021) Avcibasi, Ugur; Turkyarar, Taner; Karadag, Aysegul; Bakan, Buket; Yavasoglu, Nefise Ulku Karabay; Kusat, Kevser; Akgol, SinanThe aim of this study is the synthesis of a novel Tc-99m-labeld graft polymer and the biological evaluation of its in vitro and in vivo properties. To this end, a L-proline-graft-poly(HEMA) was prepared and labeled with Tc-99m. The radiochemical yield of approximately the Tc-99m-labeled compound amounted to 97 +/- 2.3%. The cytotoxicity test revealed no cytotoxic effect after a 24- and 48-h incubation. The results of the hemolysis test showed that hemolysis was non-toxic with an effect level of less than 2%. Subsequently, the biodistribution in healthy rats was determined. High accumulation of the polymer was observed in the pancreas, thyroid and prostate.Öğe The regulatory effects of clomiphene and tamoxifen on mTOR and LC3-II expressions in relation to autophagy in experimental polycystic ovary syndrome (PCOS)(Springer, 2022) Kuscu, Gokce Ceren; Gurel, Cevik; Buhur, Aylin; Oltulu, Fatih; Akman, Levent; Kose, Timur; Yavasoglu, Nefise Ulku KarabayBackground Polycystic ovary syndrome (PCOS) is a metabolic disease that causes infertility due to anovulation in women in reproductive age. It is known that clomiphene citrate (CC) and tamoxifen citrate (TMX) induce ovulation in women with PCOS. In this study, we aimed to investigate the effects of CC and TMX on the autophagy pathway in PCOS. Methods and results Experimental PCOS model was induced by letrozole (1 mg/kg) in rats by gavage for 21 days. After the last letrozole administration, rats were treated TMX (1 mg/kg) or CC (1 mg/kg) for 5 days. At the end of the experimental procedures, rats in all groups were sacrificed and ovarian tissues were removed. It was observed that mRNA and protein expressions of LC3-II were significantly higher in TMX and CC groups than control and PCOS groups (p < 0.05), while mRNA and protein expressions of mTOR in TMX and CC groups were found significantly lower than control and PCOS groups (p < 0.05). Conclusions In conclusion, present study suggests that TMX and CC induce autophagy in ovaries with PCOS. Autophagy is a promising target for understanding pathophysiology of this disease and for developing more effective and safe new protocols for the treatment of PCOS-related anovulation.Öğe Tetrachloromethane Induced Acute Liver Injury in Mice: Biochemical and Histopathological Study of the Hepatoprotective Effect of Hep-X Standardized Botanical Dietary Supplement(Springer, 2023) Karayildirim, Cinel Koksal; Guner, Adem; Yigitturk, Gurkan; Ince, Iskender; Yasar, Mustafa; Yavasoglu, Nefise Ulku Karabay; Yavasoglu, AltugThis work was aimed at investigating the hepatoprotective effect of Hep-X, a polyherbal formulation containing Silybum marianum L. (Milk thistle), Rosmarinus officinalis L. (Rosemary), Curcuma longa L. (Turmeric) and Fumaria officinalis L. (Fumitory) as standardized botanical dietary supplement, on mice with CCl4-induced acute liver injury. The total phenolic and flavonoid contents of Hep-X were determined as 0.125 and 0.528 mg/mL, respectively. The quercetin content was determined as 50 mu g/mL using HPLC analysis. The total antioxidant capacity showed correlation between the Hep-X concentration and percentage inhibition of free radicals. Hep-X was administered orally at 25, 50 and 100 mg/kg b.w./day against CCl4-induced hepatotoxicity in mice. The hepatic damage was measured using blood biochemical parameters. Animals upon Hep-X treatment exhibited better drug effIcacy in certain blood parameters than silymarin-treated mice. Also, Hep-X administration significantly ameliorated the liver damage by suppressing iNOS expression and apoptosis as well as by recovery of the histological structure. The obtained results suggest that Hep-X is able to significantly alleviate the hepatotoxicity induced by CCl4 in mice, which can be due to antioxidant properties of the polyherbal formulation.Öğe Viper venom induced inflammation with Montivipera xanthina (Gray, 1849) and the anti-snake venom activities of Artemisia absinthium L. in rat(Pergamon-Elsevier Science Ltd, 2013) Nalbantsoy, Ayse; Erel, Sura Baykan; Koksal, Cinel; Gocmen, Bayram; Yildiz, Mehmet Zulfu; Yavasoglu, Nefise Ulku KarabayThe present study was conducted to explore the characterization of Montivipera xanthina crude venom partially by in vitro and in vivo and the anti-snake venom activities of Artemisia absinthium L in comparison with carrageenan-induced acute inflammation model in rats. The LD50 value was estimated as 8.78 mg/kg within 24 h by different venom doses administrated intraperitoneally in mice. The IC50 value was 0.43 +/- 0.18 mu g/ml after 48 h treatment while the calculated value was 0.73 +/- 0.10 mu g/ml for the culture media totally refreshed after 2 h treatment with venom. Wistar rats were treated intraperitoneally with A. absinthium extract, 30 min before venom or carrageenan was injected subplantarly into the left hind paw. Intraperitoneal administration of 25 and 50 mg/kg extract was inhibited venom induced paw swelling at 0.5, 1, 2 and 3 h (p < 0.05) while 12.5, 25 and 50 mg/kg extract treatment was inhibited carrageenan-induced paw swelling at 2, 3, 4 and 5 h (p < 0.05). In conclusion, the in vivo toxicity and inflammatory actions and in vitro cytotoxic actions of crude M. xanthina venom were performed as a first report and inhibition of venom-induced inflammation by methanolic extract of A. absinthium was described. (C) 2013 Elsevier Ltd. All rights reserved.
