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    The analgesic effect of metformin on paclitaxel-induced neuropathic pain model in rats: By considering pathological results
    (Wolters Kluwer Medknow Publications, 2020) Hacimuftuoglu, Ahmet; Mohammadzadeh, Maryam; Taghizadehghalehjoughi, Ali; Taspinar, Numan; Togar, Basak; Nalci, Kemal Alp; Okkay, Ufuk
    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.
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    Differential effects of inhibitors of PTZ-induced kindling on glutamate transporters and enzyme expression
    (Wiley, 2021) Taspinar, Numan; Hacimuftuoglu, Ahmet; Butuner, Selcuk; Togar, Basak; Arslan, Gokhan; Taghizadehghalehjoughi, Ali; Okkay, Ufuk
    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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    Effects of processing methods and extraction solvents on the chemical content and bioactive properties of propolis
    (Springer, 2020) Bayram, Nesrin Ecem; Gercek, Yusuf Can; Bayram, Sinan; Togar, Basak
    The aim of this study was to evaluate the bioactive properties of propolis extract prepared using different solvents and different extraction methods. The extracts were analyzed by gas chromatography-mass spectrometry (GC-MS) and the differences between their antibacterial activities were evaluated by disc diffusion method. At the same time, bioactive properties of different concentrations of propolis extracts were investigated on human umbilical vein endothelial cells (HUVEC). The proliferative effects and cytotoxic effects of the extracts were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) analyzes, respectively. Total antioxidant capacity (TAC) and total oxidative status (TOS) parameters were used in assessing biochemical effects in the HUVEC cell line. The DNA damage was also analyzed by 8-oxo-2-deoxyguanosine (8-OHdG) level as indicators of genotoxicity. As a result of the MTT analysis conducted within the scope of the present study, the extracts tested were sorted as 95% ethanol extract of propolis (PEE95) > ultrasonic ethanol extract of propolis (PUEE) > 50% ethanol extract of propolis (PEE50) > ultrasonic water extract of propolis (PUWE) in terms of the effectiveness of their cell viabilities. It was observed that high concentrations of PEE95 induced LDH release. In addition to this, our findings have shown that PEE50, PUEE and PUWE increased oxidative stress at high concentrations. According to 8-OH-dG analysis, all tested extracts were found to be non-genotoxic. The results obtained from antibacterial activity and minimum inhibition concentration tests showed that PUEE and PEE95 had stronger antibacterial effects than PEE50 and PUWE. All these results indicated that propolis has beneficial effects for human health and therefore it is a valuable product which can be used as a food supplement.
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    Effects of two lichen acids isolated from Pseudevernia furfuracea (L.) Zopf in cultured human lymphocytes
    (Walter De Gruyter Gmbh, 2018) 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.
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    Inhibition of growth of U87MG human glioblastoma cells by Usnea longissima Ach.
    (Acad Brasileira De Ciencias, 2019) 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.
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    Synthesis and in Vitro Toxicity Assessment of Different Nano-Calcium Phosphate Nanoparticles
    (Inst Tecnologia Parana, 2022) Togar, Basak; Turkez, Hasan; Bakan, Feray; Arslan, Mehmet Enes; Tatar, Abdulgani; Cacciatore, Ivana; Hacimuftuoglu, Ahmet
    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.