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Item Editorial: Cell Death and Targeted Cancer Therapies(2022) Bagci-Onder, Tugba; Kutuk, Ozgur; Chonghaile, Triona Ni; Knippschild, Uwe; 000829492900001Item 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.