Fakülteler / Faculties
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Item Effects of Alendronate and Pamidronate on Apoptosis and Cell Proliferation in Cultured Primary Human Gingival Fibroblasts(2015) Soydan, S. S.; Araz, K.; Senel, F. V.; Yurtcu, E.; Helvacioglu, F.; Dagdeviren, A.; Tekindal, M. A.; Sahin, F.; 0000-0002-6026-0045; 0000-0001-8990-8282; 0000-0001-7308-9673; 0000-0003-4930-8164; 0000-0002-4060-7048; 0000-0002-4475-0861; 25636638; AAH-8887-2021; P-2877-2014; AAC-7232-2020; AAA-2998-2021; AES-7155-2022; U-9270-2018Data arising from the recent literature directed the researchers to study on the degree and extent of bisphosphonate toxicity on oral mucosa in further detail. The aim of this study is to determine the half maximal inhibitory concentration of pamidronate (PAM) and alendronate (ALN) on human gingival fibroblasts in vitro using 3-[4.5-thiazol-2-yl]-2.5-diphenyltetrazolium bromide (MTT) assay and to evaluate the effects of both agents on the proliferation and apoptotic indices. Cells used in the study were generated from human gingival specimens and divided into alendronate (n = 240), PAM (n = 240), and control groups (n = 60). Based on the MTT assay results, 10(-4), 10(-5), 10(-6), and 10(-7) M concentrations of both drugs were administered and the effects were evaluated for 6, 12, 24, 48, or 72 h periods. An indirect immunofluorescence technique was used to evaluate apoptotic (anti-caspase 3) and proliferation (anti-Ki67) indices. Toxicity of both PAM and ALN was found to be the most potent at 10(-4)-10(-5) M range. The apoptotic index of PAM group was found to be significantly higher than ALN group for all concentrations especially at 24 h incubation time (p < 0.05). The decrease in the proliferation index was found similar in first 48 h for both drugs; however, after 72 h of incubation decrease in proliferation index in PAM group was found to be significantly higher (p < 0.05). Micromolar concentrations of not only PAM but also ALN rapidly affect cells generated from human oral gingival tissue by inducing apoptosis together with inhibition of proliferation. Cytotoxic effects of both ALN and PAM on primary human gingival fibroblasts, which cause significant changes in apoptotic and proliferative indices as shown in this in vitro study, suggests that the defective epithelialization of oral mucosa is possibly a major factor on the onset of bisphosphonate-related osteonecrosis of the jaw cases.Item Experimental Study on The Effects of Massive Bowel Resection on Liver Function and Hepatocyte Apoptosis(2014) Bostanoglu, Akin; Orug, Taner; Yildiz, Baris Dogu; Isik, Sevil; Zengin, Neslihan Inci; Evren, Ebru; Saydam, Gul Sevim; 25599780Background/Aims: The effects of short-bowel syndrome on liver function and liver morphology independent of parenteral nutrition have not been thoroughly investigated. Our aim was to investigate the effects of massive bowel resection on hepatocyte apoptosis and liver function in rats. Materials and Methods: A total of 37 female Sprague-Dawley rats were randomly assigned to five groups: Control (no procedure); Sham 1 [laparotomy (LT)/enterotomy (ET); evaluated on postoperative day (POD) 1]; Sham 2 (LT/ET; evaluated on POD7; Group 1 (80% bowel resection after LT/ET; POD1); and Group 2 (80% bowel resection; POD7). Blood samples were obtained for measuring aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels. For assessing hepatocyte apoptosis, liver tissue samples from the median lobe were obtained and used for a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling assay. Results: Aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels showed statistically significant differences among the five groups. Apoptotic hepatocyte counts there were statistically significant differences among groups for counts made in 20 consecutive high-power fields. However, liver sinusoidal cell apoptosis rates among groups showed statistically significant differences for counts made in 20 consecutive highpower fields, particularly on POD7 in rats undergoing massive bowel resection. Conclusion: Parenteral nutrition is not the only factor involved in liver dysfunction after massive bowel resection. Massive bowel resection alone can cause liver abnormalities. Rats undergoing massive small intestinal resection show significant temporal increases in liver sinusoidal cell apoptosis rates.Item Effects of Intracameral Drugs and Dyes on Corneal Endothelial Cell Apoptosis in a Rat Model: An In Vivo and In Vitro Analysis(2022) Bayar, Sezin Akca; Ozturker, Zeynep Kayaarasi; Akova, Yonca Aydin; Bilezikci, Banu; Karabay, Gulten; 0000-0001-5109-755X; 36578186; AAJ-2406-2021Objectives: To evaluate the effects of intracameral drugs and dyes on rat corneal endothelial apoptosis and cell morphology. Materials and Methods: The right eyes of 72 rats were injected intracamerally with 1% lidocaine, 0.01% adrenaline, triamcinolone acetonide (TA) 4 mg/mL, 1% trypan blue (TB), 0.5% indocyanine green (ICG), and fortified balanced salt solution as control. Corneal samples were taken 1 day and 1 week post-injection. Corneal endothelial apoptosis was assessed by the TUNEL technique, and the ratio of apoptotic cells in each group was compared with the control. Corneal endothelial cell morphology was evaluated in each specimen by transmission electron microscopy. Results: The mean apoptotic endothelial cell ratio was significantly higher at 1 day and 1 week after intracameral adrenaline injection when compared to controls (p=0.03 and 0.021, respectively). TB caused a significantly higher apoptotic cell ratio when compared to controls at 1 week after injection (p=0.043). Lidocaine caused a higher apoptotic cell ratio compared to TA and ICG at 1 week, although not statistically significant (p=0.058, 0.09, 0.69, respectively). In all experimental specimens, transmission electron microscopy showed morphological changes associated with apoptosis. Conclusion: This study showed that intracameral adrenaline, TB, and lidocaine injections may have toxic effects on corneal tissue, as indicated by ultrastructural and histopathological alterations. Therefore, these agents should be used with caution in intraocular surgery.Item Prophylactic Ozone Administration Reduces Renal Ischemia-Reperfusion Injury in The Rat(2016) Kal, Oznur; Akillioglu, Ishak; Kal, Ali; Celik, Esin; Yilmaz, Mustafa; Onal, Merih; Onal, Ozkan; https://orcid.org/0000-0002-7751-4961; https://orcid.org/0000-0001-7544-5790; AAJ-7586-2021; AAJ-4936-2021Background: The objective of this study was to examine the role of ozone oxidative preconditioning after renal IR (ischemia reperfusion) injury. Methods: Twenty-eight Wistar rats were randomized into four groups: sham operated (S), IR, ozone (O), and O+IR. The S group was administered physiological saline (PS) intraperitoneally (i.p.) for seven days. The IR group was subjected to renal ischemia for 1 h by occlusion of the left renal artery and vein, followed by reperfusion for 2 h. The O group was administered ozone i.p. for seven days. In the O+IR group, ozone was administered i.p. for seven days before the IR procedure. IR injury (as in the IR group) was induced on the eight day. Laboratory analyses of renal tissue samples for superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) were performed. Results: The total oxidant score (TOS) and total antioxidant capacity (TAC) of the blood samples were also analyzed. The degree of renal injury was highest in the IR group. In the O+IR group, renal injury was decreased. The antioxidant parameters were increased in the O group. The oxidant parameters were highest in the IR group. Conclusion: Ozone preconditioning ameliorated renal IR injury, with a significant decrease observed in the renal IR injury score.Item The Protective Effect of Prophylactic Ozone Administration Against Retinal Ischemia-Reperfusion Injury(2017) Kal, Ali; Kal, Oznur; Akillioglu, Ishak; Celik, Esin; Yilmaz, Mustafa; Gonul, Saban; Solmaz, Merve; Onal, Ozkan; https://orcid.org/0000-0001-7544-5790; https://orcid.org/0000-0002-7751-4961; 27028056; AAJ-4936-2021; AAJ-7586-2021Introduction: Retinal ischemia-reperfusion (IR) injury is associated with many ocular diseases. Retinal IR injury leads to the death of retinal ganglion cells (RGCs), loss of retinal function and ultimately vision loss. The aim of this study was to show the protective effects of prophylactic ozone administration against retinal IR injury.Materials and methods: A sham group (S) (n=7) was administered physiological saline (PS) intraperitoneally (i.p.) for 7 d. An ischemia reperfusion (IR) group (n=7) was subjected to retinal ischemia followed by reperfusion for 2h. An ozone group (O) (n=7) was administered 1mg/kg of ozone i.p. for 7 d. In the ozone+IR (O+IR) group (n=7), 1mg/kg of ozone was administered i.p. for 7 d before the IR procedure and at 8 d, the IR injury was created (as in IR group). The rats were anesthetized after second hour of reperfusion and their intracardiac blood was drawn completely and they were sacrificed. Blood samples were sent to a laboratory for analysis of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total oxidant score (TOS) and total antioxidant capacity (TAC). The degree of retinal injury was evaluated according to changes in retinal cells and necrotic and apoptotic cells using the TUNEL method. Data were evaluated statistically with the Kruskal-Wallis test.Results: The number of RGCs and the inner retinal thickness were significantly decreased after ischemia, and treatment with ozone significantly inhibited retinal ischemic injury. In the IR group, the degree of retinal injury was found to be the highest. In the O+IR group, retinal injury was found to be decreased in comparison to the IR group. In the ozone group without retinal IR injury, the retinal injury score was the lowest. The differences in the antioxidant parameters SOD, GSH-Px and TAC were increased in the ozone group and the lowest in the IR group. The oxidant parameters MDA and TOS were found to be the highest in the IR group and decreased in the ozone group.Discussion: IR injury is also positively correlated with the degree of early apoptosis. This study demonstrated that ozone can attenuate subsequent ischemic damage in the rat retina through triggering the increase of the antioxidant capacity.Item Cytotoxic and Apoptotic Effects of Novel Pyrrolo[2,3-d]Pyrimidine Derivatives Containing Urea Moieties on Cancer Cell Lines(2018) Kilic-Kurt, Zuhal; Bakar-Ates, Filiz; Karakas, Bahriye; Kutuk, Ozgur; 0000-0003-2809-8946; 0000-0001-9616-4656; 0000-0001-9854-7220; 29866023; AAS-5399-2020; AAG-3843-2020; AFW-5486-2022; AAH-1671-2019Background: Pyrrolo[2,3-d]pyrimidines have been recently reported to have anticancer activities through inhibition of different targets such as, Epidermal Growth Factor Receptor (EGFR) tyrosine kinase, Janus Kinase (JAK), mitotic checkpoint protein kinase (Mps1), carbonic anhydrase, MDM-2. On the other hand, aryl urea moieties which are found in some tyrosine kinase inhibitors such as Sorafenib and Linifanib have aroused recent attention as responsible for anticancer activities. The aims of this paper are to synthesize pyrrolo[2,3-d]pyrimidine derivatives containing urea moiety and evaluate their anti-cancer activity against human lung cancer cell line (A549), prostate cancer cell line (PC3), human colon cancer cell line (SW480) and human breast cancer cell line (MCF-7). Methods: A series of new pyrrolo[2,3-d]pyrimidines containing urea moieties have been synthesized as Scheme 1. In vitro cytotoxicity of target compounds were evaluated against, SW480, PC3, A549 and MCF-7 human cancer cell lines using a MTT assay. In order to evaluate the mechanism of cytotoxic activity of compounds 9e, 10a and 10b, having the best cytotoxic activity, Annexin V binding assay, cell cycle analysis and western blot analysis were performed. Results: Among the target compounds, 10a (IC50 = 0.19 mu M) was found to be the most potent derivative against PC3 cells. Compound 10b and 9e showed the strong cytotoxic activity against MCF-7 and A549 cells with IC50 value of 1.66 mu M and 4.55 mu M, respectively. Flow cytometry data suggest that the cytotoxic activity of the compounds on cancer cells might be mediated by apoptosis revealing a significant increase in the percentage of late apoptotic cells and causing a cell cycle arrest at different stages. Western blot analysis of apoptosis marker demonstrated that these compounds induce apoptosis through the intrinsic pathway. Conclusion: Compound 9e displayed the strongest cytotoxicity against A549 cancer cell line, and induced late apoptosis in A549, as confirmed by cell cycle arrest in G0/G1 phase. In addition, compound 9e reduced expression of the anti-apoptotic protein Bcl-2 and enhanced expression of the pro-apoptotic protein Bax, besides increased caspase-9 and caspase-3, as well as cleavage of PARP levels. These results suggest that compound 9e showed a cytotoxic effect in A549 cells through activation of the mitochondrial apoptotic pathway. Further studies will be undertaken in our laboratory to improve cytotoxic activity of compound 9e and to identify the biological targets of 9e which are responsible for anticancer activity.Item Protective Effect of Spirulina on Cisplatin-Induced Ototoxicity: A Functional and Histopathological Study(2022) Tahir, Emel; Buyuklu, Adnan Fuat; Ocal, Fatma Ceyda Akin; Gurgen, Seren Gulsen; Sarsmaz, Hayrunnisa YesilObjective: The purpose of this study was to evaluate the protective effect of an antioxidant and anti-inflammatory agent, "spirulina," against cisplatin-induced ototoxicity in rats. Methods: Twenty-eight adult Sprague-Dawley rats were divided into 4 groups. Before drug administration, distortion product otoacoustic emission and auditory brainstem response tests were performed. Group 1 (n =7) received 1 mg of intraperitoneal saline. Group 2 (n=7) received a single dose of intraperitoneal cisplatin at 15 mg/kg/day. Group 3 (n=7) received oral spirulina at 1000 mg/kg/day for 10 days. Group 4 (n=7) received a single i.p. dose of cisplatin at 15 mg/kg/day, followed by 10 days of oral spirulina at 1000 mg/kg/day. The final distortion product otoacoustic emission and auditory brainstem response measurements were provided 10 days after the initial drug administration. Cochleas were removed, the histochemical examination was performed by caspase-3, caspase-9, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling methods. Results: Initially, there were no significant differences in distortion product otoacoustic emission and auditory brainstem response measurements between groups. Following cisplatin treatment, the mean difference in signal to noise ratio values was lower in the cisplatin + spirulina group compared to the cisplatin-only group. The increase in auditory brainstem response thresholds was more significant in the cisplatin-only group than in the cisplatin + spirulina group. Posttreatment auditory brainstem response latencies were prolonged in cisplatin and cisplatin + spirulina groups; however, a significant difference was obtained between these 2 groups. The cisplatin + spirulina group had a lower density of apoptotic cells than the cisplatin-only group. Conclusion: Spirulina has no adverse effects on cochlear functions and may provide some protection against cisplatin-induced ototoxicity.Item Postconditioning Ozone Alleviates Ischemia-Reperfusion Injury and Enhances Flap Endurance in Rats(2020) Elsurer, Cagdas; Onal, Merih; Selimoglu, Nebil; Erdur, Omer; Yilmaz, Mustafa; Erdogan, Ender; Kal, Oznur; Celik, Jale Bengi; Onal, Ozkan; 0000-0002-7751-4961; 30339503; AAJ-7586-2021Introduction: Muscle-flap transferring is a routine approach utilized in reconstructive operations; however, flap morbidity is often a source of post-operative difficulty. Ischemia-Reperfusion Injury (IRI) is an important contributor to the viability of flaps after transferring. The goal of this research was for assess the probable useful impacts of ozone on flap survival in a rat muscle-flap design. Materials and Methods: We examined the effects of postconditioning ozone administration on viability of pedicled composite flaps. Twenty-eight Wistar rats were randomized into four groups: sham-operated (S), ischemia-reperfusion (IR), sham-operated + ozone (O), IR + ozone (IR + O), respectively. The animals were sacrificed on the eighth day. In a general histological evaluation, flap tissues were examined with a light microscope, and apoptotic cells were counted. The Apoptotic Index (AI) was then calculated. Flap-tissue samples were sent for analyses of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and protein carbonyl (PCO), and blood samples were sent for analyses of Total Oxidant Score (TOS), and Total Antioxidant Capacity (TAC). Data were evaluated statistically using the Kruskal-Wallis test. Results: The histomorphometric score was remarkably greater in O (p = .002). The AI was greater in IR (p = .002). The antioxidant parameters values as regards SOD, GSH-Px, CAT, and TAC were found to be greater in O (p < .005). The oxidant parameters values as regards MDA, PCO, TOS were found to be greater in IR (p < .005). Discussion: The current research indicates that ozone application can attenuate the muscle-flap injury brought about by IR through triggering the increase of the antioxidant capacity.Item Assessment of the effects of radiofrequency radiation on human colon epithelium cells(2019) Tomruk, A.; Terzi, Y.K.; Guler, Ozturk G.; 0000-0001-5612-9696; 31023054; B-4372-2018OBJECTIVES: The aim of the study was to investigate the possible effects of radiofrequency radiation (RFR) at different frequencies for different exposure durations on caspase-dependent apoptosis pathways in human colon adenocarcinoma (HT-29). METHODS: HT-29 cells were exposed to 1800 MHz; 2100 MHz and 2600 MHz RFR for 3 h cont., 6 h int. and 6 h cont.. Cell viability measurements were performed by Trypan Blue exclusion assay and the gene expressions of CASP8, CASP9, CASP3 and CASP12 were analyzed using qRT-PCR. RESULTS: Exposure to 2100 MHz RFR for all 3 durations of exposures was more effective for the ratio of the number of viable HT-29 cells w.r.t 1800 MHz RFR and 2600 MHz RFR exposures. After 2100 MHz RFR exposure, caspase activation increased significantly (for 3h cont. and 6 h int. exposures CASP8 and CASP9 levels; for 6 h cont. exposure CASP3 levels) (p < 0.05). Exposures to both 1800 MHz and 2600 MHz RFR for 3 different exposure durations did not change the activation of caspases we analyzed in this study (p > 0.05). CONCLUSION: Decreases in the cell viability of HT-29 cells for certain frequencies and also durations are consistent with signifi cant increases in caspase activations. The results of caspase activation after 1800 MHz or 2600 MHz RFR exposures can be interpreted as the activation of different types of cell death pathway by caspase signaling cascades (Fig. 15, Ref. 56).Item Enhanced anticancer effect of cetuximab combined with stabilized silver ion solution in EGFR-positive lung cancer cells(2019) Ozkan, Aysun; Erdogan, Ayse; Ozkan, Odul; Manguoglu, Esra; Kiraz, NadirBackground: Cytotoxic, antiproliferative, cell cycle inhibitive, oxidative and apoptotic effects of cetuximab [antibody for epidermal growth factor receptor (EGFR)] alone and together with stabilized silver ion solution (St-Ag) on P-H1299, R-H1299, A-431 and A-549 cells were investigated. Materials and methods: Cytotoxic effects of cetuximab alone and together with St-Ag on cells were determined by Cell Titer-Blue((R)) Cell Viability and Lactate Dehydrogenase Activity tests. Cell cycle distributions and apoptosis were detected by reverse transcription polymerase chain reaction (RT-PCR). Results: St-Ag enhanced cetuximab cytotoxic effect on all cells. LDH activity, as a result of cell death, was found the highest level at treatment of cetuximab with St-Ag in all cells. Both treatment increased caspase-3/7 activity which is apoptotic enzyme was found higher in A-549 cells than other cells. Also, treatment of cetuximab with St-Ag caused increasing Bax/Bcl-2 ratio in all cells. Cetuximab with St-Ag treatment increased glutathione peroxidase activity in all cells generating oxidative stress. Proliferating Cell Nuclear Antigen (PCNA), topoisomerase II-alpha (except R-H1299), cyclin D1 and D2 genes expression were decreased in all cells which explain the cell cycle inhibition effect. Conclusion: These findings suggest that treatment of cetuximab combined with St-Ag exhibit more carcinogenesis reducing potential than cetuximab alone.