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Öğe Development of chitosan microparticles for controlled release of metoprolol tartarate(2018) Yıldız, Cenk; Demirbolat, Gülen Melike; Ergül, MustafaHypertension, defined as high blood pressure, is a common medical condition leading to cardiovascular disability andpremature deaths. Blood pressure control in an efficient way are assumed to the main targets to prevent hypertension.Since conventional dosage forms (e.g. immediate release tablets, capsules, etc.) show some limitation, greater attentionis being paid on designing the modified drug release systems. Modified release is defined as drug releasing from dosageform some time after the administration or in prolonged period of time. In this study, we aimed to design metoprololtartarate loaded chitosan microparticles to obtained modified drug release. Chitosan microparticles produced via ionicgelation with tripolyphosphate as a crosslinking agent. Prepared formulations were characterized and metoprololtartarate was loaded into the optimal blank microspheres. The entrapment efficiency, drug loading, cell viability assayand in vitro drug release were investigated. Optimum formulation was spherical and had 81% of yield and75.373±7.384?m particle size. 16 mg of metoprolol tartarate could be loaded into microparticles and drug release couldbe maintained for 48 hours.Öğe Evaluation of in vitro anticancer activity of wheat germ oil in MCF-7 breast cancer cell lines(Sivas Cumhuriyet University, 2019) Ergül, Mustafa; Bekele, Adamu; Terzi, Hatice; Altun, AhmetCancer is the main cause of death and morbidity worldwide. Among females, breast cancer is the most commonly diagnosed and the leading cause of cancer-related death. Despite an improvement in the treatment of cancer in the latest years, metastatic breast cancer treatment success is not at a desirable level. Plants have huge potential to endow us with noble drugs and current drugs of plant origin are important part of cancer chemotherapy. The aim of this study was to evaluate the antiproliferative activity of wheat germ oil in MCF-7 breast cancer cell line. Antiproliferative activity and apoptotic effect of wheat germ oil were examined using the XTT and flow cytometry assay, respectively. According to the XTT results, at concentrations greater than 0.5 mg/mL, wheat germ oil displayed significant antiproliferative activity in MCF-7 cells in a dose-dependent manner. The Annexin V binding assay results also demonstrated that the IC50 concentration of wheat germ oil increased early and late apoptotic populations (p < 0.05). Though further studies are required to specifically identify compounds involved in the anticancer activity of wheat germ oil, our findings demonstrate that wheat germ oil inhibits proliferation of MCF-7 cells and its action is dose-dependent.Öğe Investigation of anti-epileptic mechanisms of 5HT1A receptor with pentylenetetrazole induced epilepsy model in rats(Sivas Cumhuriyet University, 2019) Şahin, Bilal; Özdemir, Ercan; Taşkıran, Ahmet Şevki; Gümüş, Erkan; Ergül, MustafaObjective: According to current neurophysiological evidence, the role of 5-hydroxytryptamine (5-HT) receptors in epileptic seizure formation is still not fully elucidated. The aim of this study was to investigate the effects of 5-HT1A receptor on epileptic seizure with pentylenetetrazole induced epilepsy in rats. Method: In this study, 28 male Wistar Albino rats weighing 240-260 g were used. Pentylenetetrazole (PTZ, 35 mg/kg, i.p.) was injected to the rats to induce epilepsy and seizure stages were determined according to the Racine scale. Electrodes were placed in the skulls of the animals under stereotaxis for ECoG recording. All the experimental animals were sacrificed by decapitation after ECoG and video recordings. GABA level was measured using the Elisa kit from brain tissues, and c-Fos expression was shown immunohistochemically. Results: According to the results, it was shown that 8-OH-DPAT increased the time of initial myoclonic jerk (FMJ (p<0.05). However, the number of epileptic spikes was reduced by 8-OH-DPAT (p<0.05). GABA levels decreased in PTZ group (p<0.05). 8-OH-DPAT and WAY-100135 decreased c-Fos expression in all hippocampal areas (p<0.05). Conclusions: In conclusion, 5-HT1A receptor agonist 8-OH-DPAT, showed an anti-epileptic effect. The anti-epileptic effects of 5-HT1A receptor were found to be inconsistent with changes in GABA level. c-Fos expression is a marker of neuronal activation and may be related to the anti-convulsive effect of 5-HT1A receptor.Öğe Investigation of potential DNA damaging and apoptotic effects of PLK1 inhibitor SBE13 in breast cancer cell line MDA-MB-231(2020) Ergül, MustafaPolo-like kinase 1 (PLK1) regulates various steps of mitosis and aberrantly expressed in severaltumor types. As elevated levels of PLK1 contributes to tumorigenesis and poor prognosis,specific inhibition of PLK1 has garnered increasing attention in recent years in anticancerstudies. The objective of this study was to examine cytotoxic, apoptotic, and DNA-damagingpotentials of SBE13, a PLK1 inhibitor, against MDA-MB-231 breast cancer cells. Theregulatory efficacy of SBE13 on cell cycle arrest was also determined. Cytotoxicity of SBE13was assessed via XTT assay. Apoptosis, cell cycle distribution, and DNA damage responsewere also examined using the flow cytometry assay. The results revealed that SBE13 had adose-dependent cytotoxic effect in MDA-MB-231 cells. This compound has also induced cellcycle arrest at the G2/M point and significantly promoted apoptosis and DNA damage responsein MDA-MB-231 cells. Collectively, these data pointed out that SBE13 can be regarded as asuitable candidate for the therapy of breast cancer. However, further studies are required toconsolidate the anticancer activity of SBE13.Öğe Investigation of the potential antitumor activity of PLK1 inhibitor SBE13 in colon cancer cell line HT29(Sivas Cumhuriyet University, 2022) Gömeç, Muhammed; Yulak, Fatih; Ergül, MustafaBackground: High levels of Polo-like kinase 1 (PLK1), which are abnormally expressed in many tumor types, are known to contribute to tumorigenesis and poor prognosis. Therefore, specific targeting of PLK1 is an important strategy for cancer therapy. This study, it was aimed to investigate the cytotoxic effect of SBE13, one of the PLK1 inhibitors, against HT29 colon adenocarcinoma cells and its apoptotic potential.Methods: The cytotoxic effect of SBE13 on HT29 was determined by XTT colorimetric assay. Flow cytometry was also used to determine apoptosis.Results: SBE13 showed a dose-dependent cytotoxic effect in HT29 cells and its IC50 value was calculated as 11.79 µM for 48 h. Moreover, the Annexin V binding assay revealed that SBE13 treatment significantly increased apoptosis in HT29 cells.Conclusion: Generally, SBE13 exerts a cytotoxic effect promoted by apoptosis in colon cancer cells HT29. Although the anticancer efficacy of SBE13 in colon cancer is promising, this potential effect should be reinforced by further studies.Öğe Metforminin Tek Başına veya Valproik asit ile Beraber Farelerde Pentilentetrazol ile İndüklenen Nöbetler Üzerine Koruyucu Etkisi(Kahramanmaraş Sütçü İmam Üniversitesi, 2022) Gümüş, Erkan; Ergül, Mustafa; Gülmez, Kader; Ulu, Mustafa; Akkaya, Recep; Özdemir, Ercan; Taşkıran, Ahmet ŞevkiÖzet Amaç: Bu çalışmanın amacı, metforminin pentilentetrazol (PTZ) ile indüklenen nöbet davranışı üzerindeki etkilerini ve nöronal hasar üzerindeki nöroprotektif etkisini araştırmaktır. Gereç ve Yöntemler: 35-38 gram ağırlığındaki otuz beş (35) erkek BALB-c Albino fare rastgele beş gruba ayrıldı: Kontrol grubu (1), Salin+PTZ grubu (2), Valproik Asit (VPA 200 mg/kg i.p.)+PTZ grubu (3), Metformin (200 mg/kg i.p.)+PTZ grubu (4) ve VPA+Metformin+PTZ grubu (5). PTZ (60 mg/kg, intraperitoneal- i.p.), nöbetleri indüklemek için ilaç enjeksiyonundan 30 dakika sonra enjekte edildi ve nöbet aşamaları ve davranışsal skorlama değerlendirildi. İşlem tamamlandıktan sonra beyin dokuları çıkarıldı ve biyokimyasal ve histopatolojik prosedürlerle analiz edildi. Hipokampal Cornu Ammonis (CA)1, CA2, CA3 ve DG (dentat girus) bölgeleri histopatolojik olarak değerlendirildi ve oksidatif stres belirteçleri (toplam antioksidan durum (TAS), toplam oksidan durum (TOS)) ölçüldü. Bulgular: Salin+PTZ grubuyla karşılaştırıldığında, Metformin tek başına ilk miyoklonik jerk (FMJ) başlangıç süresini etkilemedi, ancak VPA ve metformin kombinasyonun FMJ başlangıç süresini anlamlı derecede artırdığı izlendi (p<0.05). Ek olarak, VPA ile beraber ve/veya VPA olmadan metformin tedavisi beyin oksidatif stresini önemli ölçüde azalttı (p<0.05). Ayrıca, histopatolojik değerlendirme ile metformin uygulamasının ve VPA+metformin kombinasyonunun hipokampal CA1, CA2, CA3 ve DG alanlarındaki dark nöron oluşumunu azalttığı saptandı (p<0.05). Sonuç: Metforminin, epileptik nöbetleri ve beyin oksidatif stresini azalttığı ve PTZ ile indüklenen nöbet sonrası nöral hasarı önlediği tespit edilmiştir.Öğe Nanoparticles with PDT and PTT synergistic properties working with dual NIR-light source simultaneously(2021) Sözmen, Fazlı; Küçükoflaz, Merve; Ergül, Mustafa; Şahin İnan, Deniz ZeynepA non-toxic nano system using a cleverly designed dual light can be an important treatment strategy in cancer therapy. Here, we propose a unique concept of synergistic non-toxic nanoplatform, which operates with dual light. An apoferritin nano-platform whose surface was modified with Verteporfin (Visudyne®) and with ultra-small CuS nanoparticles in the center demonstrated the synergistic effect of photodynamic therapy (PDT) and photothermal therapy (PTT). The synergistic effect of PDT and PTT were achieved with 808 nm laser light and 690 nm LED light, respectively. These results not only give a new horizon to multifunctional nanostructures for biological applications but also show a new way to design the novel PDT and PTT agents.Öğe Neuroprotective effect of astaxanthin (ATX) against cognitive impairment on PTZ-induced epileptic seizures in rats and against PTZ-induced neurotoxicity in SH-SY5Y human neuroblastoma cell culture(Sivas Cumhuriyet University, 2019) Karademir, Mustafa; Gümüş, Erkan; Taştemur, Yaşar; Ergül, Merve; Ergül, Mustafa; Karabulut, Sebahattin; Akkaya, RecepObjective: Epilepsy is a common brain disorder that seizures could cause neuronal loss in the hippocampus. Oxidative stress has an important role in the pathology of this way. The aim of this study was to investigate the neuroprotective effect of astaxanthin (ATX), on pentylenetetrazole (PTZ) induced epileptic seizures in rats and in SH-SY5Y human neuroblastoma cell culture.Method: In our study, we used 42 male 230-250 g Wistar Albino rats. Animals were divided into seven groups as control, saline (PTZ; 1 ml/kg serum physiologic), positive control (2,5 mg/kg diazepam), 10 mg/kg, 20 mg/kg, 40 mg/kg and 80 mg/kg ATX for seven days. Thirty min after the administration of the last drug at the indicated doses, PTZ was administered 45 mg/kg to induce an epileptic seizure. The animals were observed for 30 min. Seizure stages according to the Racine Scale (RC) and first myoclonic jerk times (FMJ). Twenty four hours after PTZ injection, passive avoidance test was performed, and then brain tissues were removed for biochemical and histopathological evaluation. The hippocampal Cornu Ammonis 1 (CA1), CA3 and dentate gyrus (DG) regions were evaluated histopathologically regarding neuronal damage. Besides, oxidative stress markers total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI)) were measured in brain tissues. Furthermore, ATX was performed in vitro SH-SY5Y human neuroblastoma cell culture to evaluate PTZ-induced neurotoxicity.Results: When epileptic behaviors were evaluated, ATX did not affect RC and FMJ (p>0, 05). However, ATX reduced both cognitive impairment in passive avoidance test and neuronal damage in the hippocampus (p<0, 05). Moreover, ATX reduced both TOS levels and OSI in the brain (p<0, 05). Besides of these in vitro studies, ATX increased neuronal viability in vitro. Conclusions: Although ATX does not have antiepileptic properties directly, it has a protective effect on not only in vivo but also in vitro. These effects may occur by possible oxidative pathways.Öğe Protein pump inhibitors esomeprazole and pantoprazole increase the chemosensitivity of Cml cells against imatinib(2018) Ergül, Merve; Ergül, MustafaObjective: Proton pump inhibitors (PPIs) largely used drug to treat gastroesophageal disease such as gastric ulcers.Moreover, in recent years, several studies suggest that PPIs have important anti-cancer effect in monotherapy and orcombination with chemotherapy.The aim of this study was to investigate whether esomeprazole and pantoprazole exhibit anti-cancer effect alone orcould enhance chemosensitivity of CML cell line K562 to imatinib.Method: Human chronic myeloid leukemia (CML) cells were cultured and treated with different concentrations ofesomeprazole, pantoprazole, and imatinib alone. Also these cells exposed to imatinib + esomeprazole and imatinib +pantoprazole combinations, respectively and incubated 24 h. The antiproliferative activities of the (PPIs) alone or incombination of imatinib was evaluated using the XTT colorimetric assay.Results: According to experimental data, neither PPIs showed any cytotoxicity on the K562 cell line at allconcentrations except at 500 and 1000 ?M. However, when combined with imatinib separately, they were found to havesignificant anti-cancer effects on K562 cells when compared to cell lines treated with imatinib alone (p<0.05).Conclusions: Taken together, the inhibition of V-ATPase via esomeprazole and pantoprazole might enhance thechemosensitivity of imatinib in CML cells. However, further studies are needed to be able to utilize PPIs in CML.Öğe T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells(2023) Ergül, MustafaAccumulating evidence reports that T-type calcium channels play crucial roles in tumor formation and development. However, the roles of inhibiting calcium channels in tumor cells with various inhibitors in tumor progression remain unclear. This study aimed to investigate the cytotoxic and apoptotic effects of NNC 55-0396, a T-type calcium channel inhibitor, against SNU-1 gastric cancer cells. Cytotoxic and apoptotic effects of NNC 55-0396 were evaluated by the XTT assay and flow cytometry. The results showed that NNC 55-0396 had concentration-dependent cytotoxicity in SNU-1 cells and its the half-maximal inhibitory concentration (IC50) value was calculated as 4.17 µM. The results of the Annexin V experiments also showed that this inhibitor significantly increased apoptosis in SNU-1 cells. In conclusion, these results demonstrated that NNC 55-0396 induces cytotoxic effects by increasing apoptosis in gastric cancer cells. However, further research is required for its use as a possible therapeutic agent in the treatment of gastric cancer.Öğe The Protective Effect of Hydralazine against Hydrogen Peroxide (H2O2)-Induced Oxidative Damage in C6 Glial Cell Line(Ümit Muhammet KOÇYİĞİT, 2021) Taşkıran, Ahmet Şevki; Ergül, MustafaPurpose: Recent studies have shown that hydralazine has positive effects on nervous system. However, its effect on hydrogen peroxide-induced oxidative damage in glial cells is still unclear. The current experiment was designed to examine the effect of hydralazine on glial damage after hydrogen peroxide-induced oxidative damage in C6 glial cells involving proinflammatory cytokines. Material and Methods: In this study, the C6 glioma cell line was used. Four cell groups were prepared to evaluate the effect of hydralazine on glial cell death after hydrogen peroxide-induced oxidative damage. The control group was without any treatment. Cells in the H2O2 group were treated with 0.5 mM H2O2 for 24 hours. Cells in the hydralazine group were treated with various concentrations (12.5, 25, 50, and 100 µM/mL) of hydralazine for 24 hours. Cells in the hydralazine + H2O2 group were pre-treated with various concentrations (12.5, 25 50, and 100 µM/mL) of hydralazine for 1 hour and then exposed to 0.5 mM H2O2 for 24 hours. After completing oxidative damage induction, the cell viability was evaluated XTT assay. Total antioxidant status (TAS), total oxidant status (TOS), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1 β) levels in the cells were measured by commercial kits. Results: Hydralazine at the concentrations of 50 and 100 µM/mL significantly increased the cell viability in C6 cells after hydrogen peroxide-induced oxidative damage (p < 0.001). It also significantly decreased the levels of TOS (p < 0.001) whereas rising TAS levels (p < 0.01) after hydrogen peroxide-induced oxidative damage. Moreover, hydralazine reduced TNF-α and IL-1 β levels in C6 cells after hydrogen peroxide-induced oxidative damage (P < 0.001). Conclusion: Hydralazine decreases glial cell death after hydrogen peroxide-induced oxidative damage in C6 cells by activating antioxidant system and inhibiting proinflammatory cytokines.Öğe Unraveling the Role of Apoptosis in the Antiproliferative Activity of ?-Glucan on A549 Cells(2023) Joha, Zıad; Ergül, MustafaPrevious studies have reported the anticancer properties of ?-glucan on various cancer cells. The objective of this research was to investigate the involvement of apoptosis in the cytotoxic action of ?-glucan on the A549 cells. The cytotoxic impact of this drug on A549 cells was examined by subjecting them to various quantities of the substance, and the XTT assay was utilized to determine cell survival. Flow cytometry was performed to investigate apoptosis. A statistically significant and dose-dependent cytotoxic impact on A549 cells was observed upon treatment with ?-glucan. The calculated IC50 value of ?-glucan for A549 cells after a 24-hour treatment period was discovered to be 82.16 ?g/mL. Further investigations carried out using the IC50 dose of ?-glucan revealed a significant increase in the late apoptotic cells percentage. The capacity of ?-glucan to trigger apoptosis is thought to be the cause of its cytotoxic action on lung cancer. The revelation of this discovery emphasizes the promising possibilities of ?-glucan as an effective therapeutic choice.
