Sürdürülebilir Kalkınma Amaçları
Yayınlar
- MakaleAçık Erişim2022Scopus SJRQ2Synthesis and in Vitro Toxicity Assessment of Different Nano-Calcium Phosphate Nanoparticles
Togar, Basak; Türkez, Hasan; Bakan, Feray; Arslan, Mehmet Enes; Tatar, Abdulgani; Cacciatore, Ivana; Hacimüftüoglu, Ahmet; Çadirci, Kenan; Stefano, Di Antonio; Mardinoglu, Adil
Nanoscale biomaterials are commonly used in a wide range of biomedical applications such as bone graft substitutes, gene delivery systems, and biologically active agents. On the other hand, the cytotoxic potential of these particles hasn't yet been studied comprehensively to understand whether or not they exert any negative impact on the cellular structures. Here, we undertook the synthesis of beta-tricalcium phosphate (beta-TCP) and biphasic tricalcium phosphate (BCP) nanoparticles (NPs) and determine their concentration-dependent toxic effects in human fetal osteoblastic (hFOB 1.19) cell line. Firstly, BCP and beta-TCP were synthesized using a water-based precipitation technique and characterized by X-Ray Diffraction (XRD), Raman Spectroscopy, and Transmission Electron Microscopy (TEM). The cytological effects of beta-TCP and BCP at different concentrations (0-640 ppm) were evaluated by using 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. The total oxidative status (TOS) parameter was used for investigating oxidative stress potentials of the NPs. In addition, the study assessed the DNA damage product 8-hydroxy-2'-deoxyguanosine (8-Oxo-dG) level in hFOB 1.19 cell cultures. The results indicated that the beta-TCP (above 320 ppm) and BCP (above 80 ppm) NPs exhibited cytotoxicity effects on high concentrations. It was also observed that the oxidative stress increased relatively as the concentrations of NPs increased, aligning with the cytotoxicity results. However, the NPs concentrations of 160 ppm and above increased the level of 8-OH-dG. Consequently, there is a need for more systematic in vivo and in vitro approaches to the toxic effects of both nanoparticles.
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İncele - MakaleYalnız künye2021Scopus SJRQ2Differential effects of inhibitors of PTZ-induced kindling on glutamate transporters and enzyme expression
Taspinar, Numan; Hacimuftuoglu, Ahmet; Butuner, Selcuk; Togar, Basak; Arslan, Gokhan; Taghizadehghalehjoughi, Ali; Okkay, Ufuk; Agar, Erdal; Stephens, Robert, Jr.; Turkez, Hasan
Epilepsy is a neurological disorder resulting from abnormal neuronal firing in the brain. Glutamate transporters and the glutamate-glutamine cycle play crucial roles in the development of seizures. In the present study, the correlation of epilepsy with glutamate transporters and enzymes was investigated. Herein, male Wistar rats were randomly allocated into four groups (six animals/group); 35 mg/kg pentylenetetrazole (PTZ) was used to induce a kindling model of epilepsy. Once the kindling model was established, animals were treated for 15 days with either valproic acid (VPA, 350 mg/kg) or ceftriaxone (CEF, 200 mg/kg) in addition to the control group receiving saline. After treatment, electrocorticography (ECoG) was performed to record the electrical activity of the cerebral cortex. The glutamate reuptake time (T-80) was also determined in situ using an in vivo voltammetry. The expression levels of glutamate transporters and enzymes in the M1 and CA3 areas of the brain were determined using a real-time polymerase chain reaction (RT-PCR). ECoG measurements showed that the mean spike number of the PTZ + VPA and PTZ + CEF groups was significantly lower (p < 0.05) than that of the PTZ group. Compared with the PTZ group, VPA or CEF treatment decreased the glutamate reuptake time (T-80). The expression levels of EAAC1, GLT-1, GLAST, glutamine synthetase (GS), and glutaminase were increased in the PTZ group. Treatment with VPA or CEF enhanced the expression levels of GLT-1, GLAST, EAAC1, and GS, whereas the glutaminase expression level was reduced. The current results suggest that VPA or CEF decreases seizure activity by increasing glutamate reuptake by upregulating GLT-1 and GLAST expression, implying a possible mechanism for treating epilepsy. Also, we have suggested a novel mechanism for the antiepileptic activity of VPA via decreasing glutaminase expression levels. To our knowledge, this is the first study to measure the glutamate reuptake time in situ during the seizure (i.e., real-time measurement).
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İncele - MakaleAçık Erişim2020Scopus SJRQ3The analgesic effect of metformin on paclitaxel-induced neuropathic pain model in rats: By considering pathological results
Hacimuftuoglu, Ahmet; Mohammadzadeh, Maryam; Hjoughi, Ali Taghizadehghale; Taspinar, Numan; Togar, Basak; Nalci, Kemal Alp; Okkay, Ufuk; Gundogdu, Betul
Background and Objective: Metformin (MET) has been used as an antidiabetic agent for type II diabetes. At the same time, recent researches have shown that the clinical improvement of MET is useful for nerve damage. In this study, we investigated the analgesic effect of MET in paclitaxel (PAC)-induced neuropathic pain. Materials and Methods: Forty-two adult, female rats, Wistar strain weighing 220 ± 10 g were randomly divided into 5 experimental groups. PAC was intraperitoneally (IP) administered (2.0 mg/kg) for 4 groups every other day (0, 2, 4, and 6 days). By the 30th day, MET (100, 200, and 400 mg/kg) was administered to 4 groups. Before and after treatment, basal pain threshold values were measured with Randall-Selitto analgesiometer test. At the end of experiment, pathological values were measured in selected regions including brain (motor cortex, M1), spinal cord (L4-L5), sciatic nerve, and muscle. Results: According to our results, PAC-induced neuropathic pain reached to highest level at 14th day. Four hundred milligram/kilogram concentration of MET remarkably decreased PAC-induced neuropathic pain. On the other hand, pathologic features have shown that PAC had significant pathological change in the brain and spinal cord while in the peripheral nerves and muscles had not shown any pathological change. Conclusion: The pathological results of the current study for the first time demonstrated that MET beside of its antidiabetic effects reversed neuropathic pain induced by PAC. Consequently, this research can be promising for cancer patients that suffering from neuropathic pain induced by anticancer drugs.
AtıfScopus12WoS12OpenAlex13İncele - MakaleAçık Erişim2019Scopus SJRQ1Inhibition of growth of U87MG human glioblastoma cells by Usnea longissima Ach.
Emsen, Bugrahan; Ozdemir, Ozlem; Engin, Tubanur; Togar, Basak; Cavusoglu, Seyda; Turkez, Hasan
Herbal medicines are efficient to reduce side effects in the fight against glioblastoma, which plays a critical role within brain cancer species. The recent studies designated for testing the effects of lichens that have shown numerous anticancer activities on glioblastoma so far. In the present study, different concentrations of water extract obtained from Usnea longissima Ach. were used in order to determine cytotoxic (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase tests), antioxidant (via total antioxidant capacity test), pro-oxidant (via total oxidant status test) and genotoxic (via 8-hydroxy-2'-deoxyguanosine test) effects of them on human U87MG-glioblastoma cancer cell lines. Primary mixed glial-neuronal non-cancerous cells from Sprague-Dawley rats were also utilized to measure the effects of treatments on non-cancerous cells. Based on median inhibitory concentration values, the data belonged to non-cancerous cells (2486.71 mg/L) showed distinct towering compared to U87MG (80.93 mg/L) cells. The viability of non-cancerous and U87MG cells exposed to extract is decreased in a dose dependent manner. It was also showed that low concentrations of extract notably increased total antioxidant capacity on non-cancerous cells. In addition, various phenolic compounds in extract were detected through high-perfonnance liquid chromatography. The recent results encourage that extract will be able to have therapeutic potential against glioblastoma.
AtıfScopus23WoS20OpenAlex21İncele - MakaleAçık Erişim2018Scopus SJRQ3Effects of two lichen acids isolated from Pseudevernia furfuracea (L.) Zopf in cultured human lymphocytes
Emsen, Bugrahan; Togar, Basak; Turkez, Hasan; Aslan, Ali
The present study aims at assessing the efficacies of olivetoric acid (OA) and physodic acid (PA) isolated from Pseudevernia furfuracea (L.) Zopf (Parmeliaceae) in human lymphocytes (HLs) in vitro. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays were performed to establish cytotoxicity in HLs. Besides, oxidative stress and genotoxicity were monitored by estimating the changes of total oxidative stress (TOS) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) levels, respectively, in HLs. At the same time, OA- and PA-induced total antioxidant capacity (TAC) levels in HLs were determined. Although especially low concentrations of OA (IC50 = 109.94 mg/L) and PA (IC50 = 665.49 mg/L) did not show cytotoxic effect at high levels in HLs, it was revealed that cytotoxicity was significantly (p < 0.05) associated with oxidative stress and genotoxicity via correlation analysis. While TOS level in HLs did not statistically (p > 0.05) increase in the presence of all treatments (0.5-100 mg/L) of PA, TAC level was increased by PA applications in certain concentrations (0.5-10 mg/L). Overall, the obtained data indicate that OA and especially PA as lichen compounds that do not cause oxidative stress can be a new resource of therapeutics as recognized in the present study with their high antioxidant features.
AtıfWoS20OpenAlex24İncele - Proje2016Beyin Hastalıklarının Tanı ve Tedavisinde Yeni Yöntem: İn Vivo Mikrosensör Teknolojisi
Kufrevioglu, Omer Irfan; Taspinar, Numan; Binnetoğlu, Damla; Sengul, Goksin; Togar, Basak; Malkoc, Ismail; Denkbaş, Emir Baki; Ozcan, Halil; Okkay, Ufuk; Nalci, Kemal Alp
Beyin hastalıklarının birçoğunun sinaptik aralıklarda görev yapan nörotransmitterlerin beyindeki bazal seviyelerindeki değişiklikler veya sinaptik aralıktan uzaklaştırılma parametrelerinde gelişen aksaklıklar sonucu oluştuğu düşünülmektedir. Bu proje kapsamında beyin hastalıklarının tanı, tedavi ve izleminde kullanılmak üzere gerekli biyouyumlu sensör, kablosuz nörotransmitter algılama cihazı ve yeni bir yazılım üretilmiştir. Beyin nörotransmitter konsantrasyonlarını algılayabilen biyouyumlu sensörlerimizin fabrikasyonu üç aşamadan oluşmaktadır. Bunlar sırasıyla mikroelektrotların fotolitografik yöntemlerle üretimi, paketlenmesi ve seçici kimyasal bariyerlerle kaplanmasıdır. Üretilen sensörler düşük maliyetli ve biyouyumludur. Uyguladığımız yeni bariyerler selektivite ve sensitivite değerlerini yükseltmiştir. Ürettiğimiz sensörlerden gelen konsantrasyon bilgisine ilişkin akımın işlenmesinde kullanılan cihaz bu proje kapsamında üretilmiştir. Bu cihaz, nA seviyesindeki nörotransmitter konsantrasyonu kaynaklı akımları 107 kat yükseltmektedir. Üretilen cihaz, denekler üzerinde taşınabilmesi için oldukça küçük ve hafif olarak tasarlanmıştır. Bu cihaz, bataryası ile birlikte toplam 11.8 g ağırlığında ve 2.9 cm x 2.4 cm boyutundadır. Geliştirilen cihazdan gelen bilgiler deney ve takip esnasında işlenip hem grafik olarak hem de gerçek zamanlı analiz sonuçları olarak ekrana yansıtılabilmektedir. Labview tabanlı yazılıma bu bilgiler kablosuz haberleşme ünitesi vasıtasıyla iletilmektedir. Ayrıca, filtreleme çalışmaları sayesinde sistemin gürültü performansı iyileştirilmiştir. Geliştirdiğimiz bu sistem, deneysel olarak sıçanlarda oluşturduğumuz Depresyon, Kronik Ağrı, Hepatik Ensefalopati, Epilepsi, Alzheimer hastalığı hayvan modellerinde denenmiş, glutamat ve diğer nörotransmitterlerin ölçümleri in-vivo voltametrik olarak yapılmıştır. Burada değişikliği tespit edilen nörotransmitterlerin cinsine göre ilaçlar seçilmiş ve farklılıklar ortadan kaldırılmaya çalışılmıştır. Çok sayıda ilaç denemeleri yapılmıştır. Başarılı bulunanlara sonuç raporunda yer verilmiştir. Bu sonuçlara göre beyin hastalıklarının birçoğunun nörotransmitter değişimleriyle ilişkili olabileceği gösterilmiştir. Bu nörotransmitterlere yönelik tedavilerin de hastalıkların klinik gidişatında düzelmelere yol açtığı tespit edilmiştir. Bu proje ile beyin hastalıklarının etiyolojilerine yönelik çok sayıda veri sunulmakta hatta tedavilerine ışık tutulabilmektedir. Cihaz, yazılım ve sensör için patent başvurusunda bulunulmuştur. Ayrıca bu proje kapsamında TÜBİTAK desteği belirtilen 1 Doktora, 5 Yüksek Lisans tezi bitirilmiştir. 4 Doktora, 3 yüksek lisans tezi bitme aşamasındadır.
